Variant 1-30874473-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014654.4(SDC3):c.986C>T(p.Thr329Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0352 in 1,614,092 control chromosomes in the GnomAD database, including 9,101 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.047 ( 984 hom., cov: 32)

Exomes 𝑓: 0.034 ( 8117 hom. )

Consequence

SDC3
NM_014654.4 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 2.79

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.3020973E-4).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SDC3	NM_014654.4 linkuse as main transcript	c.986C>T	p.Thr329Ile	missense_variant	4/5	ENST00000339394.7
SDC3	XM_011542463.1 linkuse as main transcript	c.953C>T	p.Thr318Ile	missense_variant	4/5
SDC3	XM_011542464.3 linkuse as main transcript	c.950C>T	p.Thr317Ile	missense_variant	4/5
SDC3	XM_011542466.2 linkuse as main transcript	c.860C>T	p.Thr287Ile	missense_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC3	ENST00000339394.7 linkuse as main transcript	c.986C>T	p.Thr329Ile	missense_variant	4/5	1	NM_014654.4	P1
SDC3	ENST00000336798.11 linkuse as main transcript	c.812C>T	p.Thr271Ile	missense_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.0474

AC:

7203

AN:

152118

Hom.:

974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0975

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00417

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0927

AC:

23307

AN:

251464

Hom.:

3783

AF XY:

0.0856

AC XY:

11629

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0182

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.537

Gnomad SAS exome

AF:

0.0972

Gnomad FIN exome

AF:

0.0947

Gnomad NFE exome

AF:

0.00622

Gnomad OTH exome

AF:

0.0555

GnomAD4 exome

AF:

0.0340

AC:

49660

AN:

1461856

Hom.:

8117

Cov.:

AF XY:

0.0349

AC XY:

25396

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.0940

Gnomad4 FIN exome

AF:

0.0844

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.0467

GnomAD4 genome

AF:

0.0475

AC:

7225

AN:

152236

Hom.:

984

Cov.:

AF XY:

0.0564

AC XY:

4195

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.540

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.0975

Gnomad4 NFE

AF:

0.00420

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0233

Hom.:

1440

Bravo

AF:

0.0501

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.0184

AC:

ESP6500EA

AF:

0.00430

AC:

ExAC

AF:

0.0858

AC:

10416

Asia WGS

AF:

0.254

AC:

883

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Obesity, association with

Other:1

association, no assertion criteria provided

literature only

OMIM

May 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.076

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.00033

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.69

.;N

MutationTaster

Benign

0.21

P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.53

N;N

REVEL

Benign

0.066

Sift

Benign

0.45

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.19

B;B

Vest4

0.044

MPC

0.072

ClinPred

0.011

GERP RS

3.9

Varity_R

0.041

gMVP

0.18

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