Genetic Variant NM_014654.4:c.907G>A (chr1-30874552-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_014654.4(SDC3):c.907G>A(p.Asp303Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,856 control chromosomes in the GnomAD database, including 33,040 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.22 ( 4274 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28766 hom. )

Consequence

SDC3
NM_014654.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.46

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=0.004136145).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC3	NM_014654.4 link	c.907G>A	p.Asp303Asn	missense_variant	Exon 4 of 5	ENST00000339394.7	NP_055469.3	O75056
SDC3	XM_011542463.1 link	c.874G>A	p.Asp292Asn	missense_variant	Exon 4 of 5		XP_011540765.1
SDC3	XM_011542464.3 link	c.871G>A	p.Asp291Asn	missense_variant	Exon 4 of 5		XP_011540766.1
SDC3	XM_011542466.2 link	c.781G>A	p.Asp261Asn	missense_variant	Exon 4 of 5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC3	ENST00000339394.7 link	c.907G>A	p.Asp303Asn	missense_variant	Exon 4 of 5	1	NM_014654.4	ENSP00000344468.6		O75056
SDC3	ENST00000336798.11 link	c.733G>A	p.Asp245Asn	missense_variant	Exon 2 of 3	1		ENSP00000338346.7		A0A9K3Y886

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33799

AN:

151956

Hom.:

4267

Cov.:

show subpopulations

Gnomad AFR

AF:

0.330

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.0493

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.208

GnomAD3 exomes

AF:

0.185

AC:

46551

AN:

251266

Hom.:

5049

AF XY:

0.192

AC XY:

26068

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.117

Gnomad EAS exome

AF:

0.0490

Gnomad SAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.186

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.193

AC:

281912

AN:

1461780

Hom.:

28766

Cov.:

AF XY:

0.196

AC XY:

142444

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.340

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.0396

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.191

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.223

AC:

33841

AN:

152076

Hom.:

4274

Cov.:

AF XY:

0.222

AC XY:

16482

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.0496

Gnomad4 SAS

AF:

0.297

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.207

Alfa

AF:

0.198

Hom.:

4333

Bravo

AF:

0.222

TwinsUK

AF:

0.177

AC:

656

ALSPAC

AF:

0.189

AC:

729

ESP6500AA

AF:

0.310

AC:

1367

ESP6500EA

AF:

0.182

AC:

1565

ExAC

AF:

0.194

AC:

23542

Asia WGS

AF:

0.162

AC:

565

AN:

3478

EpiCase

AF:

0.184

EpiControl

AF:

0.177

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

.;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.050

Sift

Uncertain

0.0010

D;D

Sift4G

Benign

0.30

T;T

Polyphen

0.0080

B;B

Vest4

0.042

MPC

0.066

ClinPred

0.039

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.094

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over