rs1539360

chr1-30873352-G-Achr1-30873352-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014654.4(SDC3):c.1188C>T(p.Gly396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,612,534 control chromosomes in the GnomAD database, including 9,309 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.080 (653 hom., cov: 32)
  • Exomes 𝑓: 0.10 (8656 hom.)
• Consequence: SDC3 NM_014654.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-0.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDC3	NM_014654.4	c.1188C>T	p.Gly396=	synonymous_variant	5/5	ENST00000339394.7
SDC3	XM_011542463.1	c.1155C>T	p.Gly385=	synonymous_variant	5/5
SDC3	XM_011542464.3	c.1152C>T	p.Gly384=	synonymous_variant	5/5
SDC3	XM_011542466.2	c.1062C>T	p.Gly354=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDC3	ENST00000339394.7	c.1188C>T	p.Gly396=	synonymous_variant	5/5	1	NM_014654.4	P1
SDC3	ENST00000336798.11	c.1014C>T	p.Gly338=	synonymous_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12232 AN: 152010 Hom.: 653 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.0567

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.0767

GnomAD3 exomes AF: 0.0892 AC: 22399 AN: 251216 Hom.: 1166 AF XY: 0.0910 AC XY: 12350 AN XY: 135778

Gnomad AFR exome AF: 0.0175

Gnomad AMR exome AF: 0.0434

Gnomad ASJ exome AF: 0.0881

Gnomad EAS exome AF: 0.0799

Gnomad SAS exome AF: 0.0616

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.0968

GnomAD4 exome AF: 0.105 AC: 153303 AN: 1460406 Hom.: 8656 Cov.: 31 AF XY: 0.104 AC XY: 75309 AN XY: 726590

Gnomad4 AFR exome AF: 0.0148

Gnomad4 AMR exome AF: 0.0452

Gnomad4 ASJ exome AF: 0.0860

Gnomad4 EAS exome AF: 0.0594

Gnomad4 SAS exome AF: 0.0626

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.0977

GnomAD4 genome AF: 0.0804 AC: 12231 AN: 152128 Hom.: 653 Cov.: 32 AF XY: 0.0792 AC XY: 5891 AN XY: 74358

Gnomad4 AFR AF: 0.0206

Gnomad4 AMR AF: 0.0622

Gnomad4 ASJ AF: 0.0806

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0769

Alfa AF: 0.0988 Hom.: 539

Bravo AF: 0.0741

Asia WGS AF: 0.0810 AC: 280 AN: 3478

EpiCase AF: 0.116

EpiControl AF: 0.114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	9.9
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs1539360; hg19: chr1-31346199; COSMIC: COSV59579312; COSMIC: COSV59579312;