dbSNP rs16933090: SOX6:c.-5+42068G>A (chr11-16434247-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033326.3(SOX6):c.-5+42068G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,992 control chromosomes in the GnomAD database, including 1,159 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1159 hom., cov: 32)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

SOX6
NM_033326.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

9 publications found

Variant links:

Genes affected

SOX6 (HGNC:16421): (SRY-box transcription factor 6) This gene encodes a member of the D subfamily of sex determining region y-related transcription factors that are characterized by a conserved DNA-binding domain termed the high mobility group box and by their ability to bind the minor groove of DNA. The encoded protein is a transcriptional activator that is required for normal development of the central nervous system, chondrogenesis and maintenance of cardiac and skeletal muscle cells. The encoded protein interacts with other family members to cooperatively activate gene expression. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]

SOX6 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Tolchin-Le Caignec syndrome
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

SOX6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033326.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX6	NM_033326.3		c.-5+42068G>A		intron	N/A	NP_201583.2	P35712-3
	SOX6	NM_001367872.1		c.-4-92995G>A		intron	N/A	NP_001354801.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SOX6	ENST00000396356.7	TSL:1	c.-5+42068G>A	intron	N/A	ENSP00000379644.3	P35712-3
SOX6	ENST00000529469.1	TSL:4	c.-108G>A	5_prime_UTR	Exon 1 of 2	ENSP00000432596.1	E9PQ67
SOX6	ENST00000887067.1		c.-5+42068G>A	intron	N/A	ENSP00000557126.1

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17827

AN:

151866

Hom.:

1155

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0226

Gnomad SAS

AF:

0.0500

Gnomad FIN

AF:

0.0993

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.120

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.167

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.117

AC:

17852

AN:

151984

Hom.:

1159

Cov.:

AF XY:

0.115

AC XY:

8561

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.163

AC:

6746

AN:

41448

American (AMR)

AF:

0.101

AC:

1538

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

429

AN:

3472

East Asian (EAS)

AF:

0.0227

AC:

117

AN:

5164

South Asian (SAS)

AF:

0.0500

AC:

241

AN:

4818

European-Finnish (FIN)

AF:

0.0993

AC:

1049

AN:

10560

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7405

AN:

67934

Other (OTH)

AF:

0.118

AC:

250

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

782

1564

2347

3129

3911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.110

Hom.:

4125

Bravo

AF:

0.118

Asia WGS

AF:

0.0540

AC:

192

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.0

(source)

DANN

Benign

0.32

PhyloP100

-1.1

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over