rs2491132

Variant names:

• chr1-30876800-C-T
• rs2491132
• NM_014654.4:c.622G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-30876800-C-T
• chr1-30876800-C-A
• chr1-30876800-C-G

Variant summary

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

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
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -1.92
• 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=0.0026866794).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 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.622G>A	p.Val208Ile	missense	Exon 3 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.622G>A	p.Val208Ile	missense	Exon 3 of 5	ENSP00000344468.6	O75056
	SDC3	ENST00000336798.11	TSL:1	c.448G>A	p.Val150Ile	missense	Exon 1 of 3	ENSP00000338346.7	A0A9K3Y886
	SDC3	ENST00000937355.1		c.574G>A	p.Val192Ile	missense	Exon 3 of 5	ENSP00000607414.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22362 AN: 152036 Hom.: 2194 Cov.: 32

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

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.: 36 AF XY: 0.194 AC XY: 139580 AN XY: 719544

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

GnomAD4 genome AF: 0.147 AC: 22357 AN: 152154 Hom.: 2193 Cov.: 32 AF XY: 0.142 AC XY: 10578 AN XY: 74374

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: 25 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15239 AN: 67946

Other (OTH) AF: 0.135 AC: 286 AN: 2112

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

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	0.061
BayesDel_addAF	Benign	-0.85	T
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	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-1.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.0030
Sift	Benign	0.68	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.0060
MPC		0.057
ClinPred		0.0059	T
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)

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: rs2491132; hg19: chr1-31349647; COSMIC: COSV108158638; COSMIC: COSV108158638;