1-30874592-C-T

Variant names:

• chr1-30874592-C-T
• rs188640187
• NM_014654.4:c.871-4G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014654.4(SDC3):​c.871-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SDC3 NM_014654.4 splice_region, intron
• Scores: Splicing: ADA: 0.0001808
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC3	NM_014654.4	c.871-4G>A		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000339394.7	NP_055469.3
SDC3	XM_011542463.1	c.838-4G>A		splice_region_variant, intron_variant	Intron 3 of 4		XP_011540765.1
SDC3	XM_011542464.3	c.835-4G>A		splice_region_variant, intron_variant	Intron 3 of 4		XP_011540766.1
SDC3	XM_011542466.2	c.745-4G>A		splice_region_variant, intron_variant	Intron 3 of 4		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC3	ENST00000339394.7	c.871-4G>A		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_014654.4	ENSP00000344468.6
SDC3	ENST00000336798.11	c.697-4G>A		splice_region_variant, intron_variant	Intron 1 of 2	1		ENSP00000338346.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000801 AC: 2 AN: 249574 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460706 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726572

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.0
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.014
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

LitVar

Other links and lift over

dbSNP: rs188640187; hg19: chr1-31347439;