Variant 13-112068140-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005986.3(SOX1):c.482T>C(p.Val161Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000386 in 984,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

SOX1
NM_005986.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10523185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX1	NM_005986.3 linkuse as main transcript	c.482T>C	p.Val161Ala	missense_variant	1/1	ENST00000330949.3
SOX1-OT	NR_120392.1 linkuse as main transcript	n.85-27335T>C		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.482T>C	p.Val161Ala	missense_variant	1/1		NM_005986.3	P1
SOX1-OT	ENST00000658904.1 linkuse as main transcript	n.168+10957T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000498

AC:

AN:

140542

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000626

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000367

AC:

AN:

844292

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

400844

show subpopulations

Gnomad4 AFR exome

AF:

0.0000624

Gnomad4 AMR exome

AF:

0.00

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:

0.0000352

Gnomad4 OTH exome

AF:

0.000131

GnomAD4 genome

AF:

0.0000498

AC:

AN:

140542

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

68418

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000626

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

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

Mar 21, 2022

The c.482T>C (p.V161A) alteration is located in exon 1 (coding exon 1) of the SOX1 gene. This alteration results from a T to C substitution at nucleotide position 482, causing the valine (V) at amino acid position 161 to be replaced by an alanine (A). 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

Benign

0.094

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.088

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.39

M_CAP

Pathogenic

0.36

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.88

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.22

REVEL

Benign

0.068

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.015

Vest4

0.079

MutPred

0.44

Gain of catalytic residue at V159 (P = 0);

MVP

0.20

ClinPred

0.085

GERP RS

2.9

Varity_R

0.067

gMVP

0.49

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