Variant 1-30876800-C-T 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.622G>A(p.Val208Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 1,601,094 control chromosomes in the GnomAD database, including 33,054 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2193 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30861 hom. )

Consequence

SDC3
NM_014654.4 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -1.92

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:

SDC3 (HGNC:):

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=0.0026866794).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC3	NM_014654.4 linkuse as main transcript	c.622G>A	p.Val208Ile	missense_variant	3/5	ENST00000339394.7	NP_055469.3	O75056
SDC3	XM_011542463.1 linkuse as main transcript	c.589G>A	p.Val197Ile	missense_variant	3/5		XP_011540765.1
SDC3	XM_011542464.3 linkuse as main transcript	c.586G>A	p.Val196Ile	missense_variant	3/5		XP_011540766.1
SDC3	XM_011542466.2 linkuse as main transcript	c.496G>A	p.Val166Ile	missense_variant	3/5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SDC3	ENST00000339394.7 linkuse as main transcript	c.622G>A	p.Val208Ile	missense_variant	3/5	1	NM_014654.4	ENSP00000344468.6	O75056
SDC3	ENST00000336798.11 linkuse as main transcript	c.448G>A	p.Val150Ile	missense_variant	1/3	1		ENSP00000338346.7	A0A9K3Y886
SDC3	ENST00000471567.1 linkuse as main transcript	n.556G>A		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22362

AN:

152036

Hom.:

2194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.0462

Gnomad SAS

AF:

0.0688

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.150

AC:

36131

AN:

240746

Hom.:

3369

AF XY:

0.152

AC XY:

19881

AN XY:

130380

show subpopulations

Gnomad AFR exome

AF:

0.0336

Gnomad AMR exome

AF:

0.0830

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.0496

Gnomad SAS exome

AF:

0.0789

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.216

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.197

AC:

285138

AN:

1448940

Hom.:

30861

Cov.:

AF XY:

0.194

AC XY:

139580

AN XY:

719544

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.0890

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.0345

Gnomad4 SAS exome

AF:

0.0824

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.147

AC:

22357

AN:

152154

Hom.:

2193

Cov.:

AF XY:

0.142

AC XY:

10578

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0382

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.0463

Gnomad4 SAS

AF:

0.0693

Gnomad4 FIN

AF:

0.181

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.198

Hom.:

4564

Bravo

AF:

0.137

TwinsUK

AF:

0.205

AC:

761

ALSPAC

AF:

0.217

AC:

836

ESP6500AA

AF:

0.0418

AC:

184

ESP6500EA

AF:

0.211

AC:

1813

ExAC

AF:

0.153

AC:

18555

Asia WGS

AF:

0.0680

AC:

239

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

0.061

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0030

DANN

Benign

0.78

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.52

T;T

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.46

.;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.0030

Sift

Benign

0.68

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0

B;B

Vest4

0.0060

MPC

0.057

ClinPred

0.0059

GERP RS

-8.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.080

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