Genetic Variant SOX13:p.Gly80Arg (chr1-204114339-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005686.3(SOX13):c.238G>C(p.Gly80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G80C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SOX13
NM_005686.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.890

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054852337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX13	NM_005686.3 link	c.238G>C	p.Gly80Arg	missense_variant	Exon 3 of 14	ENST00000367204.6	NP_005677.2	Q9UN79
SOX13	XM_047435006.1 link	c.238G>C	p.Gly80Arg	missense_variant	Exon 3 of 14		XP_047290962.1
SOX13	XM_005245623.4 link	c.238G>C	p.Gly80Arg	missense_variant	Exon 3 of 14		XP_005245680.1
SOX13	XM_047435007.1 link	c.238G>C	p.Gly80Arg	missense_variant	Exon 3 of 14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX13	ENST00000367204.6 link	c.238G>C	p.Gly80Arg	missense_variant	Exon 3 of 14	1	NM_005686.3	ENSP00000356172.1		Q9UN79

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.00

AC:

AN:

43840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25948

East Asian (EAS)

AF:

0.00

AC:

AN:

39548

South Asian (SAS)

AF:

0.00

AC:

AN:

84858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108608

Other (OTH)

AF:

0.00

AC:

AN:

60148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Uncertain

0.098

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.67

.;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Uncertain

0.049

MutationAssessor

Benign

0.0

N;.;N

PhyloP100

0.89

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.1

N;N;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0040

D;D;.

Sift4G

Benign

0.27

T;T;T

Polyphen

0.026

B;.;B

Vest4

0.15

MutPred

0.10

Gain of glycosylation at P84 (P = 0.1125);Gain of glycosylation at P84 (P = 0.1125);Gain of glycosylation at P84 (P = 0.1125);

MVP

0.16

MPC

0.031

ClinPred

0.11

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.045

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over