dbSNP rs2282440: SDC3:p.Thr329Ile (chr1-30874473-G-A) – 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.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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.047 ( 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

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=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 rank	MANE	Protein	UniProt
SDC3	NM_014654.4 link	c.986C>T	p.Thr329Ile	missense_variant	Exon 4 of 5	ENST00000339394.7	NP_055469.3	O75056
SDC3	XM_011542463.1 link	c.953C>T	p.Thr318Ile	missense_variant	Exon 4 of 5		XP_011540765.1
SDC3	XM_011542464.3 link	c.950C>T	p.Thr317Ile	missense_variant	Exon 4 of 5		XP_011540766.1
SDC3	XM_011542466.2 link	c.860C>T	p.Thr287Ile	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.986C>T	p.Thr329Ile	missense_variant	Exon 4 of 5	1	NM_014654.4	ENSP00000344468.6		O75056
SDC3	ENST00000336798.11 link	c.812C>T	p.Thr271Ile	missense_variant	Exon 2 of 3	1		ENSP00000338346.7		A0A9K3Y886

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

GnomAD2 exomes

AF:

0.0927

AC:

23307

AN:

251464

AF XY:

0.0856

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 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

African (AFR)

AF:

0.0151

AC:

507

AN:

33480

American (AMR)

AF:

0.187

AC:

8371

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0180

AC:

470

AN:

26134

East Asian (EAS)

AF:

0.559

AC:

22187

AN:

39698

South Asian (SAS)

AF:

0.0940

AC:

8111

AN:

86252

European-Finnish (FIN)

AF:

0.0844

AC:

4506

AN:

53416

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00236

AC:

2626

AN:

1112000

Other (OTH)

AF:

0.0467

AC:

2823

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2265

4530

6796

9061

11326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.0475

AC:

7225

AN:

152236

Hom.:

984

Cov.:

AF XY:

0.0564

AC XY:

4195

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0184

AC:

764

AN:

41546

American (AMR)

AF:

0.108

AC:

1649

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3470

East Asian (EAS)

AF:

0.540

AC:

2782

AN:

5156

South Asian (SAS)

AF:

0.115

AC:

557

AN:

4826

European-Finnish (FIN)

AF:

0.0975

AC:

1034

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00420

AC:

286

AN:

68026

Other (OTH)

AF:

0.0412

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

268

536

804

1072

1340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0234

Hom.:

1618

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

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

0.11

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

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

PhyloP100

2.8

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

Mutation Taster

=97/3

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