Variant 1-30876560-C-T 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_014654.4(SDC3):c.862G>A(p.Val288Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000132 in 1,517,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SDC3
NM_014654.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.360

Variant links:

Genes affected

SDC3 (HGNC:10660): (syndecan 3) The protein encoded by this gene belongs to the syndecan proteoglycan family. It may play a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism. Allelic variants of this gene have been associated with obesity. [provided by RefSeq, Oct 2009]

SDC3 links:

Genome browser will be placed here

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=0.0442051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC3	NM_014654.4 link	c.862G>A	p.Val288Met	missense_variant	3/5	ENST00000339394.7	NP_055469.3	O75056
SDC3	XM_011542463.1 link	c.829G>A	p.Val277Met	missense_variant	3/5		XP_011540765.1
SDC3	XM_011542464.3 link	c.826G>A	p.Val276Met	missense_variant	3/5		XP_011540766.1
SDC3	XM_011542466.2 link	c.736G>A	p.Val246Met	missense_variant	3/5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC3	ENST00000339394.7 link	c.862G>A	p.Val288Met	missense_variant	3/5	1	NM_014654.4	ENSP00000344468.6		O75056
SDC3	ENST00000336798.11 link	c.688G>A	p.Val230Met	missense_variant	1/3	1		ENSP00000338346.7		A0A9K3Y886

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.33e-7

AC:

AN:

1364886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668522

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:

0.0000178

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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

Feb 10, 2022

The c.862G>A (p.V288M) alteration is located in exon 3 (coding exon 3) of the SDC3 gene. This alteration results from a G to A substitution at nucleotide position 862, causing the valine (V) at amino acid position 288 to be replaced by a methionine (M). 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

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.24

.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

.;L

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.029

Sift

Benign

0.080

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0030

B;B

Vest4

0.038

MutPred

0.25

.;Gain of glycosylation at P292 (P = 0.1334);

MVP

0.068

MPC

0.067

ClinPred

0.10

GERP RS

0.27

Varity_R

0.031

gMVP

0.14

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

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