rs2282440

Variant names:

• chr1-30874473-G-A
• rs2282440
• NM_014654.4:c.986C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-30874473-G-A
• chr1-30874473-G-C
• chr1-30874473-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 2.79
• Publications: 28 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014654.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC3	NM_014654.4	MANE Select	c.986C>T	p.Thr329Ile	missense	Exon 4 of 5	NP_055469.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC3	ENST00000339394.7	TSL:1 MANE Select	c.986C>T	p.Thr329Ile	missense	Exon 4 of 5	ENSP00000344468.6	O75056
	SDC3	ENST00000336798.11	TSL:1	c.812C>T	p.Thr271Ile	missense	Exon 2 of 3	ENSP00000338346.7	A0A9K3Y886
	SDC3	ENST00000937355.1		c.938C>T	p.Thr313Ile	missense	Exon 4 of 5	ENSP00000607414.1

Frequencies

GnomAD3 genomes AF: 0.0474 AC: 7203 AN: 152118 Hom.: 974 Cov.: 32

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

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.: 33 AF XY: 0.0349 AC XY: 25396 AN XY: 727242

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: 59 AN: 5766

European-Non Finnish (NFE) AF: 0.00236 AC: 2626 AN: 1112000

Other (OTH) AF: 0.0467 AC: 2823 AN: 60394

GnomAD4 genome AF: 0.0475 AC: 7225 AN: 152236 Hom.: 984 Cov.: 32 AF XY: 0.0564 AC XY: 4195 AN XY: 74412

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: 62 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: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00420 AC: 286 AN: 68026

Other (OTH) AF: 0.0412 AC: 87 AN: 2112

Alfa AF: 0.0234 Hom.: 1618

Bravo AF: 0.0501

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.0184 AC: 81

ESP6500EA AF: 0.00430 AC: 37

ExAC AF: 0.0858 AC: 10416

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Obesity, association with (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.10
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.00033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.066
Sift	Benign	0.45	T
Sift4G	Benign	0.23	T
Polyphen		0.19	B
Vest4		0.044
MPC		0.072
ClinPred		0.011	T
GERP RS		3.9
Varity_R		0.041
gMVP		0.18
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2282440; hg19: chr1-31347320; COSMIC: COSV107412129; COSMIC: COSV107412129;