Variant 1-204114323-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005686.3(SOX13):c.222C>A(p.Asp74Glu) variant causes a missense, splice region 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SOX13
NM_005686.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.797

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04637766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SOX13	NM_005686.3 linkuse as main transcript	c.222C>A	p.Asp74Glu	missense_variant, splice_region_variant	3/14	ENST00000367204.6	NP_005677.2
SOX13	XM_047435006.1 linkuse as main transcript	c.222C>A	p.Asp74Glu	missense_variant, splice_region_variant	3/14		XP_047290962.1
SOX13	XM_005245623.4 linkuse as main transcript	c.222C>A	p.Asp74Glu	missense_variant, splice_region_variant	3/14		XP_005245680.1
SOX13	XM_047435007.1 linkuse as main transcript	c.222C>A	p.Asp74Glu	missense_variant, splice_region_variant	3/14		XP_047290963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX13	ENST00000367204.6 linkuse as main transcript	c.222C>A	p.Asp74Glu	missense_variant, splice_region_variant	3/14	1	NM_005686.3	ENSP00000356172	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1442178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716610

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

Cov.:

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

Mar 11, 2022

The c.222C>A (p.D74E) alteration is located in exon 3 (coding exon 2) of the SOX13 gene. This alteration results from a C to A substitution at nucleotide position 222, causing the aspartic acid (D) at amino acid position 74 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

0.10

BayesDel_addAF

Benign

-0.0057

BayesDel_noAF

Benign

-0.25

CADD

Benign

7.1

DANN

Benign

0.47

DEOGEN2

Benign

0.082

T;T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.32

.;T;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.046

T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

0.14

N;.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.28

N;N;.

REVEL

Uncertain

0.33

Sift

Benign

0.93

T;T;.

Sift4G

Benign

0.71

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.13

MutPred

0.20

Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);

MVP

0.17

MPC

0.027

ClinPred

0.063

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.037

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

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