Variant 1-204123202-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005686.3(SOX13):c.1225A>G(p.Met409Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOX13
NM_005686.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.460

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06086144).

BP6

Variant 1-204123202-A-G is Benign according to our data. Variant chr1-204123202-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2266994.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SOX13	NM_005686.3 link	c.1225A>G	p.Met409Val	missense_variant	11/14	ENST00000367204.6	NP_005677.2	Q9UN79
SOX13	XM_047435006.1 link	c.1225A>G	p.Met409Val	missense_variant	11/14		XP_047290962.1
SOX13	XM_005245623.4 link	c.1222A>G	p.Met408Val	missense_variant	11/14		XP_005245680.1
SOX13	XM_047435007.1 link	c.1222A>G	p.Met408Val	missense_variant	11/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SOX13	ENST00000367204.6 link	c.1225A>G	p.Met409Val	missense_variant	11/14	1	NM_005686.3	ENSP00000356172.1	Q9UN79
SOX13	ENST00000618875.4 link	c.1225A>G	p.Met409Val	missense_variant	10/13	1		ENSP00000478239.1	Q9UN79
SOX13	ENST00000272193.10 link	n.1092A>G		non_coding_transcript_exon_variant	8/11	2
SOX13	ENST00000525258.1 link	n.669A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000822

AC:

AN:

1460316

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.015

BayesDel_noAF

Benign

-0.26

CADD

Benign

0.63

DANN

Benign

0.53

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.75

.;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.061

T;T

MetaSVM

Uncertain

-0.092

MutationAssessor

Benign

1.9

L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

N;.

REVEL

Benign

0.23

Sift

Benign

0.46

T;.

Sift4G

Benign

0.81

T;T

Polyphen

0.0

B;B

Vest4

0.19

MutPred

0.18

Gain of catalytic residue at M409 (P = 0.032);Gain of catalytic residue at M409 (P = 0.032);

MVP

0.53

MPC

0.31

ClinPred

0.045

GERP RS

-6.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.070

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over