Genetic Variant SOX6:c.-5+66664G>A (chr11-16409651-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 ENST00000396356.7(SOX6):c.-5+66664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 151,816 control chromosomes in the GnomAD database, including 304 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 0.056 ( 304 hom., cov: 32)

Consequence

SOX6
ENST00000396356.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0180

Publications

2 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):

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

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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.083 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX6	NM_033326.3 link	c.-5+66664G>A		intron_variant	Intron 1 of 15		NP_201583.2	P35712-3
SOX6	NM_001367872.1 link	c.-4-68399G>A		intron_variant	Intron 3 of 16		NP_001354801.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
SOX6	ENST00000396356.7 link	c.-5+66664G>A	intron_variant	Intron 1 of 15	1	ENSP00000379644.3	P35712-3
SOX6	ENST00000529469.1 link	c.-5+24493G>A	intron_variant	Intron 1 of 1	4	ENSP00000432596.1	E9PQ67
SOX6	ENST00000530378.5 link	n.-5+66664G>A	intron_variant	Intron 5 of 9	2	ENSP00000432577.1	E9PQ78
SOX6	ENST00000533658.5 link	n.333+56050G>A	intron_variant	Intron 4 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0564

AC:

8559

AN:

151698

Hom.:

304

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0393

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0154

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0847

Gnomad OTH

AF:

0.0513

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0564

AC:

8561

AN:

151816

Hom.:

304

Cov.:

AF XY:

0.0563

AC XY:

4180

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.0145

AC:

602

AN:

41428

American (AMR)

AF:

0.0393

AC:

599

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

167

AN:

3470

East Asian (EAS)

AF:

0.000582

AC:

AN:

5158

South Asian (SAS)

AF:

0.0152

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.116

AC:

1212

AN:

10490

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0848

AC:

5757

AN:

67894

Other (OTH)

AF:

0.0508

AC:

107

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

399

798

1198

1597

1996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0763

Hom.:

834

Bravo

AF:

0.0491

Asia WGS

AF:

0.00811

AC:

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.4

(source)

DANN

Benign

0.38

PhyloP100

-0.018

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over