chr1-204123149-G-A

Position:

chr1-204123149-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005686.3(SOX13):c.1172G>A(p.Arg391Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,616 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 1 hom. )

Consequence

SOX13
NM_005686.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13956976).

BS2

High AC in GnomAdExome4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SOX13	NM_005686.3 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	11/14	ENST00000367204.6	NP_005677.2
SOX13	XM_047435006.1 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	11/14		XP_047290962.1
SOX13	XM_005245623.4 linkuse as main transcript	c.1169G>A	p.Arg390Gln	missense_variant	11/14		XP_005245680.1
SOX13	XM_047435007.1 linkuse as main transcript	c.1169G>A	p.Arg390Gln	missense_variant	11/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SOX13	ENST00000367204.6 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	11/14	1	NM_005686.3	ENSP00000356172	P1
SOX13	ENST00000618875.4 linkuse as main transcript	c.1172G>A	p.Arg391Gln	missense_variant	10/13	1		ENSP00000478239	P1
SOX13	ENST00000272193.10 linkuse as main transcript	n.1039G>A		non_coding_transcript_exon_variant	8/11	2
SOX13	ENST00000525258.1 linkuse as main transcript	n.616G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000402

AC:

AN:

248952

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135072

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.000116

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:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000198

AC:

AN:

1461418

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00000810

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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

Alfa

AF:

0.0000494

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000413

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

May 27, 2022

The c.1172G>A (p.R391Q) alteration is located in exon 11 (coding exon 10) of the SOX13 gene. This alteration results from a G to A substitution at nucleotide position 1172, causing the arginine (R) at amino acid position 391 to be replaced by a glutamine (Q). 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

0.076

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.092

Eigen_PC

Benign

0.075

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

.;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.14

T;T

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.83

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.23

N;.

REVEL

Benign

0.22

Sift

Benign

0.44

T;.

Sift4G

Benign

0.61

T;T

Polyphen

0.059

B;B

Vest4

0.43

MVP

0.42

MPC

1.0

ClinPred

0.075

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.085

gMVP

0.38

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