Variant chr13-112067786-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005986.3(SOX1):c.128G>A(p.Gly43Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000166 in 1,203,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G43C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

SOX1
NM_005986.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

Variant links:

Genes affected

SOX1 (HGNC:11189): (SRY-box transcription factor 1) This intronless 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. In mice, a similar protein regulates the gamma-crystallin genes and is essential for lens development. [provided by RefSeq, Jul 2008]

SOX1 links:

SOX1-OT (HGNC:42733): (SOX1 overlapping transcript)

SOX1-OT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42234904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX1	NM_005986.3 linkuse as main transcript	c.128G>A	p.Gly43Asp	missense_variant	1/1	ENST00000330949.3
SOX1-OT	NR_120392.1 linkuse as main transcript	n.85-27689G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX1	ENST00000330949.3 linkuse as main transcript	c.128G>A	p.Gly43Asp	missense_variant	1/1		NM_005986.3	P1
SOX1-OT	ENST00000658904.1 linkuse as main transcript	n.168+10603G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000140

AC:

AN:

143146

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000731

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000143

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000166

AC:

AN:

1203856

Hom.:

Cov.:

AF XY:

0.00000170

AC XY:

AN XY:

587792

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000457

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.128G>A (p.G43D) alteration is located in exon 1 (coding exon 1) of the SOX1 gene. This alteration results from a G to A substitution at nucleotide position 128, causing the glycine (G) at amino acid position 43 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.12

Eigen_PC

Benign

0.027

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.33

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.42

MetaSVM

Pathogenic

0.92

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.97

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.51

Sift

Benign

0.053

Sift4G

Benign

0.25

Polyphen

0.99

Vest4

0.27

MutPred

0.32

Gain of catalytic residue at G39 (P = 0);

MVP

0.66

ClinPred

0.33

GERP RS

2.4

Varity_R

0.068

gMVP

0.89

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

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