1-30876623-C-G

Position:

• chr1-30876623-C-G

Variant summary

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

The NM_014654.4(SDC3):​c.799G>C​(p.Glu267Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDC3 NM_014654.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.996

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 (MetaRNN=0.059378654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDC3	NM_014654.4	c.799G>C	p.Glu267Gln	missense_variant	3/5	ENST00000339394.7	NP_055469.3
SDC3	XM_011542463.1	c.766G>C	p.Glu256Gln	missense_variant	3/5		XP_011540765.1
SDC3	XM_011542464.3	c.763G>C	p.Glu255Gln	missense_variant	3/5		XP_011540766.1
SDC3	XM_011542466.2	c.673G>C	p.Glu225Gln	missense_variant	3/5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDC3	ENST00000339394.7	c.799G>C	p.Glu267Gln	missense_variant	3/5	1	NM_014654.4	ENSP00000344468.6
SDC3	ENST00000336798.11	c.625G>C	p.Glu209Gln	missense_variant	1/3	1		ENSP00000338346.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.799G>C (p.E267Q) alteration is located in exon 3 (coding exon 3) of the SDC3 gene. This alteration results from a G to C substitution at nucleotide position 799, causing the glutamic acid (E) at amino acid position 267 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	.;L
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.025
Sift	Benign	0.076	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.040	B;B
Vest4		0.045
MutPred		0.31		.;Gain of glycosylation at T264 (P = 0.0968);
MVP		0.093
MPC		0.067
ClinPred		0.16	T
GERP RS		3.0
Varity_R		0.066
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-31349470;