chr1-30873224-T-C

Variant names:

• chr1-30873224-T-C
• NM_014654.4:c.1316A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014654.4(SDC3):​c.1316A>G​(p.Glu439Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 8.02

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC3	NM_014654.4	c.1316A>G	p.Glu439Gly	missense_variant	Exon 5 of 5	ENST00000339394.7	NP_055469.3
SDC3	XM_011542463.1	c.1283A>G	p.Glu428Gly	missense_variant	Exon 5 of 5		XP_011540765.1
SDC3	XM_011542464.3	c.1280A>G	p.Glu427Gly	missense_variant	Exon 5 of 5		XP_011540766.1
SDC3	XM_011542466.2	c.1190A>G	p.Glu397Gly	missense_variant	Exon 5 of 5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC3	ENST00000339394.7	c.1316A>G	p.Glu439Gly	missense_variant	Exon 5 of 5	1	NM_014654.4	ENSP00000344468.6
SDC3	ENST00000336798.11	c.1142A>G	p.Glu381Gly	missense_variant	Exon 3 of 3	1		ENSP00000338346.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1316A>G (p.E439G) alteration is located in exon 5 (coding exon 5) of the SDC3 gene. This alteration results from a A to G substitution at nucleotide position 1316, causing the glutamic acid (E) at amino acid position 439 to be replaced by a glycine (G). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.88	.;D
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Uncertain	-0.055	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.87
MutPred		0.77		.;Loss of stability (P = 0.1157);
MVP		0.71
MPC		0.078
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.77
gMVP		0.76

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: chr1-31346071;