1-204123114-C-G

Position:

chr1-204123114-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005686.3(SOX13):c.1137C>G(p.Asp379Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SOX13
NM_005686.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10847324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX13	NM_005686.3 link	c.1137C>G	p.Asp379Glu	missense_variant, splice_region_variant	11/14	ENST00000367204.6	NP_005677.2	Q9UN79
SOX13	XM_047435006.1 link	c.1137C>G	p.Asp379Glu	missense_variant, splice_region_variant	11/14		XP_047290962.1
SOX13	XM_005245623.4 link	c.1134C>G	p.Asp378Glu	missense_variant, splice_region_variant	11/14		XP_005245680.1
SOX13	XM_047435007.1 link	c.1134C>G	p.Asp378Glu	missense_variant, splice_region_variant	11/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOX13	ENST00000367204.6 link	c.1137C>G	p.Asp379Glu	missense_variant, splice_region_variant	11/14	1	NM_005686.3	ENSP00000356172.1	Q9UN79
SOX13	ENST00000618875.4 link	c.1137C>G	p.Asp379Glu	missense_variant, splice_region_variant	10/13	1		ENSP00000478239.1	Q9UN79
SOX13	ENST00000272193.10 link	n.1004C>G		splice_region_variant, non_coding_transcript_exon_variant	8/11	2
SOX13	ENST00000525258.1 link	n.581C>G		splice_region_variant, non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248962

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135064

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:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461124

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000826

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

Sep 12, 2023

The c.1137C>G (p.D379E) alteration is located in exon 11 (coding exon 10) of the SOX13 gene. This alteration results from a C to G substitution at nucleotide position 1137, causing the aspartic acid (D) at amino acid position 379 to be replaced by a glutamic acid (E). 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

0.15

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.099

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.59

.;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.11

T;T

MetaSVM

Uncertain

-0.014

MutationAssessor

Benign

1.3

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.29

N;.

REVEL

Uncertain

0.30

Sift

Benign

0.58

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0050

B;B

Vest4

0.26

MutPred

0.14

Gain of methylation at K378 (P = 0.0872);Gain of methylation at K378 (P = 0.0872);

MVP

0.60

MPC

0.29

ClinPred

0.26

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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