Variant chr1-204122336-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005686.3(SOX13):c.961C>T(p.Arg321Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000896 in 1,562,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

SOX13
NM_005686.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

Variant links:

Genes affected

SOX13 (HGNC:11192): (SRY-box transcription factor 13) This 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 cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. It has also been determined to be a type-1 diabetes autoantigen, also known as islet cell antibody 12. [provided by RefSeq, Jul 2008]

SOX13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SOX13	NM_005686.3 linkuse as main transcript	c.961C>T	p.Arg321Cys	missense_variant	9/14	ENST00000367204.6	NP_005677.2
SOX13	XM_047435006.1 linkuse as main transcript	c.961C>T	p.Arg321Cys	missense_variant	9/14		XP_047290962.1
SOX13	XM_005245623.4 linkuse as main transcript	c.958C>T	p.Arg320Cys	missense_variant	9/14		XP_005245680.1
SOX13	XM_047435007.1 linkuse as main transcript	c.958C>T	p.Arg320Cys	missense_variant	9/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX13	ENST00000367204.6 linkuse as main transcript	c.961C>T	p.Arg321Cys	missense_variant	9/14	1	NM_005686.3	ENSP00000356172	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000567

AC:

AN:

176506

Hom.:

AF XY:

0.0000106

AC XY:

AN XY:

94736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000137

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000851

AC:

AN:

1410004

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

697778

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

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:

0.0000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000168

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

Dec 15, 2022

The c.961C>T (p.R321C) alteration is located in exon 9 (coding exon 8) of the SOX13 gene. This alteration results from a C to T substitution at nucleotide position 961, causing the arginine (R) at amino acid position 321 to be replaced by a cysteine (C). 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

0.084

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.92

.;D

M_CAP

Pathogenic

0.33

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Pathogenic

0.98

MutationAssessor

Uncertain

2.0

M;M

MutationTaster

Benign

0.99

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.4

N;.

REVEL

Uncertain

0.47

Sift

Uncertain

0.023

D;.

Sift4G

Uncertain

0.051

T;T

Polyphen

1.0

D;D

Vest4

0.56

MutPred

0.19

Gain of catalytic residue at P320 (P = 0.0112);Gain of catalytic residue at P320 (P = 0.0112);

MVP

0.64

MPC

0.73

ClinPred

0.74

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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