Genetic Variant SDC3:p.Val208Ile (chr1-30876800-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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

Publications

28 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SDC3	NM_014654.4 link	c.622G>A	p.Val208Ile	missense_variant	Exon 3 of 5	ENST00000339394.7	NP_055469.3	O75056
SDC3	XM_011542463.1 link	c.589G>A	p.Val197Ile	missense_variant	Exon 3 of 5		XP_011540765.1
SDC3	XM_011542464.3 link	c.586G>A	p.Val196Ile	missense_variant	Exon 3 of 5		XP_011540766.1
SDC3	XM_011542466.2 link	c.496G>A	p.Val166Ile	missense_variant	Exon 3 of 5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDC3	ENST00000339394.7 link	c.622G>A	p.Val208Ile	missense_variant	Exon 3 of 5	1	NM_014654.4	ENSP00000344468.6	O75056
SDC3	ENST00000336798.11 link	c.448G>A	p.Val150Ile	missense_variant	Exon 1 of 3	1		ENSP00000338346.7	A0A9K3Y886
SDC3	ENST00000471567.1 link	n.556G>A		non_coding_transcript_exon_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.150

AC:

36131

AN:

240746

AF XY:

0.152

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 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

African (AFR)

AF:

0.0298

AC:

985

AN:

33074

American (AMR)

AF:

0.0890

AC:

3856

AN:

43310

Ashkenazi Jewish (ASJ)

AF:

0.139

AC:

3511

AN:

25234

East Asian (EAS)

AF:

0.0345

AC:

1365

AN:

39522

South Asian (SAS)

AF:

0.0824

AC:

7019

AN:

85162

European-Finnish (FIN)

AF:

0.202

AC:

10675

AN:

52866

Middle Eastern (MID)

AF:

0.0924

AC:

523

AN:

5660

European-Non Finnish (NFE)

AF:

0.223

AC:

246686

AN:

1104398

Other (OTH)

AF:

0.176

AC:

10518

AN:

59714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

12666

25332

37999

50665

63331

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8222

16444

24666

32888

41110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22357

AN:

152154

Hom.:

2193

Cov.:

AF XY:

0.142

AC XY:

10578

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0382

AC:

1585

AN:

41536

American (AMR)

AF:

0.127

AC:

1945

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

512

AN:

3470

East Asian (EAS)

AF:

0.0463

AC:

240

AN:

5184

South Asian (SAS)

AF:

0.0693

AC:

334

AN:

4822

European-Finnish (FIN)

AF:

0.181

AC:

1922

AN:

10590

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15239

AN:

67946

Other (OTH)

AF:

0.135

AC:

286

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

924

1848

2771

3695

4619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

246

492

738

984

1230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.194

Hom.:

9598

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

May 01, 2019

OMIM

Significance:association

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

(source)

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

PhyloP100

-1.9

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over