Variant 1-204121964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005686.3(SOX13):c.840G>A(p.Met280Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000758 in 1,609,414 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 3 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SOX13
NM_005686.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0138973).

BS2

High AC in GnomAd4 at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SOX13	NM_005686.3 linkuse as main transcript	c.840G>A	p.Met280Ile	missense_variant	8/14	ENST00000367204.6
SOX13	XM_047435006.1 linkuse as main transcript	c.840G>A	p.Met280Ile	missense_variant	8/14
SOX13	XM_005245623.4 linkuse as main transcript	c.837G>A	p.Met279Ile	missense_variant	8/14
SOX13	XM_047435007.1 linkuse as main transcript	c.837G>A	p.Met279Ile	missense_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SOX13	ENST00000367204.6 linkuse as main transcript	c.840G>A	p.Met280Ile	missense_variant	8/14	1	NM_005686.3	P1
SOX13	ENST00000618875.4 linkuse as main transcript	c.840G>A	p.Met280Ile	missense_variant	7/13	1		P1
SOX13	ENST00000272193.10 linkuse as main transcript	n.707G>A		non_coding_transcript_exon_variant	5/11	2
SOX13	ENST00000480326.1 linkuse as main transcript	c.*65G>A		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000110

AC:

AN:

246008

Hom.:

AF XY:

0.0000672

AC XY:

AN XY:

134004

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1457220

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

725044

show subpopulations

Gnomad4 AFR exome

AF:

0.000899

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000493

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000538

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.000509

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000108

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 16, 2023

The c.840G>A (p.M280I) alteration is located in exon 8 (coding exon 7) of the SOX13 gene. This alteration results from a G to A substitution at nucleotide position 840, causing the methionine (M) at amino acid position 280 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.088

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.096

M_CAP

Benign

0.054

MetaRNN

Benign

0.014

T;T

MetaSVM

Uncertain

-0.063

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.29

N;.

REVEL

Benign

0.23

Sift

Benign

0.41

T;.

Sift4G

Benign

0.47

T;T

Polyphen

0.0010

B;B

Vest4

0.17

MutPred

0.19

Loss of ubiquitination at K275 (P = 0.0806);Loss of ubiquitination at K275 (P = 0.0806);

MVP

0.23

MPC

0.33

ClinPred

0.0043

GERP RS

2.8

Varity_R

0.051

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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