NM_006941.4:c.249C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_006941.4(SOX10):c.249C>T(p.Tyr83Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,610,100 control chromosomes in the GnomAD database, including 570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 299 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 271 hom. )

Consequence

SOX10
NM_006941.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.95

Publications

8 publications found

Variant links:

Genes affected

SOX10 (HGNC:11190): (SRY-box transcription factor 10) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development. Mutations in this gene are associated with Waardenburg-Shah and Waardenburg-Hirschsprung disease. [provided by RefSeq, Jul 2008]

SOX10 links:

POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

POLR2F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 22-37983536-G-A is Benign according to our data. Variant chr22-37983536-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 227079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.95 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SOX10	NM_006941.4 link	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 2 of 4	ENST00000396884.8	NP_008872.1
POLR2F	NM_001301130.2 link	c.294-2618G>A		intron_variant	Intron 4 of 5		NP_001288059.1
POLR2F	NM_001363825.1 link	c.*38+11226G>A		intron_variant	Intron 5 of 5		NP_001350754.1
POLR2F	NM_001301131.2 link	c.293+16366G>A		intron_variant	Intron 4 of 4		NP_001288060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX10	ENST00000396884.8 link	c.249C>T	p.Tyr83Tyr	synonymous_variant	Exon 2 of 4	1	NM_006941.4	ENSP00000380093.2

Frequencies

GnomAD3 genomes

AF:

0.0347

AC:

5275

AN:

152190

Hom.:

297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0191

GnomAD2 exomes

AF:

0.00918

AC:

2222

AN:

242016

AF XY:

0.00673

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000432

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00365

AC:

5319

AN:

1457792

Hom.:

271

Cov.:

AF XY:

0.00312

AC XY:

2265

AN XY:

725186

show subpopulations

African (AFR)

AF:

0.125

AC:

4167

AN:

33420

American (AMR)

AF:

0.00552

AC:

245

AN:

44390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26056

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39566

South Asian (SAS)

AF:

0.000245

AC:

AN:

85836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51654

Middle Eastern (MID)

AF:

0.00348

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000332

AC:

369

AN:

1110914

Other (OTH)

AF:

0.00824

AC:

496

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

297

594

892

1189

1486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0347

AC:

5292

AN:

152308

Hom.:

299

Cov.:

AF XY:

0.0332

AC XY:

2474

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.121

AC:

5050

AN:

41564

American (AMR)

AF:

0.0109

AC:

167

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000471

AC:

AN:

68010

Other (OTH)

AF:

0.0189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

246

491

737

982

1228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.0392

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Tyr83Tyr in exon 2 of SOX10: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 11.3% (496/4406) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs73415876). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 05, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Sep 14, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PCWH syndrome

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Waardenburg syndrome

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

3.0

PromoterAI

0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Mutation Taster

=85/15

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over