Variant chr11-15986197-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001367873.1(SOX6):c.2183+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,613,764 control chromosomes in the GnomAD database, including 230 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 15 hom., cov: 32)

Exomes 𝑓: 0.016 ( 215 hom. )

Consequence

SOX6
NM_001367873.1 splice_region, intron

Scores

Splicing: ADA: 0.00004457

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.359

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-15986197-T-C is Benign according to our data. Variant chr11-15986197-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-15986197-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0119 (1805/152282) while in subpopulation NFE AF= 0.0186 (1264/68010). AF 95% confidence interval is 0.0177. There are 15 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1805 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX6	NM_001367873.1 linkuse as main transcript	c.2183+7A>G		splice_region_variant, intron_variant		ENST00000683767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX6	ENST00000683767.1 linkuse as main transcript	c.2183+7A>G		splice_region_variant, intron_variant			NM_001367873.1	A2	P35712-1

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1808

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0128

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00830

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0186

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0114

AC:

2862

AN:

251030

Hom.:

AF XY:

0.0112

AC XY:

1516

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00844

Gnomad ASJ exome

AF:

0.00983

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00121

Gnomad FIN exome

AF:

0.0105

Gnomad NFE exome

AF:

0.0184

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0158

AC:

23141

AN:

1461482

Hom.:

215

Cov.:

AF XY:

0.0153

AC XY:

11129

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.00877

Gnomad4 ASJ exome

AF:

0.00907

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0188

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0119

AC:

1805

AN:

152282

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

800

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00394

Gnomad4 AMR

AF:

0.0128

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00830

Gnomad4 NFE

AF:

0.0186

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.0151

Hom.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 21, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 05, 2020	- -

SOX6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000045

dbscSNV1_RF

Benign

0.15

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over