chr1-30874473-G-T

Variant names:

• chr1-30874473-G-T
• rs2282440
• NM_014654.4:c.986C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014654.4(SDC3):​c.986C>A​(p.Thr329Lys) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T329I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDC3 NM_014654.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10093528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC3	NM_014654.4	c.986C>A	p.Thr329Lys	missense_variant	Exon 4 of 5	ENST00000339394.7	NP_055469.3
SDC3	XM_011542463.1	c.953C>A	p.Thr318Lys	missense_variant	Exon 4 of 5		XP_011540765.1
SDC3	XM_011542464.3	c.950C>A	p.Thr317Lys	missense_variant	Exon 4 of 5		XP_011540766.1
SDC3	XM_011542466.2	c.860C>A	p.Thr287Lys	missense_variant	Exon 4 of 5		XP_011540768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDC3	ENST00000339394.7	c.986C>A	p.Thr329Lys	missense_variant	Exon 4 of 5	1	NM_014654.4	ENSP00000344468.6
SDC3	ENST00000336798.11	c.812C>A	p.Thr271Lys	missense_variant	Exon 2 of 3	1		ENSP00000338346.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0086
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N
PhyloP100		2.8
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.11
Sift	Benign	0.12	T;T
Sift4G	Benign	0.99	T;T
Polyphen		0.32	B;B
Vest4		0.11
MutPred		0.46		.;Gain of ubiquitination at T329 (P = 0.0051);
MVP		0.082
MPC		0.080
ClinPred		0.29	T
GERP RS		3.9
Varity_R		0.072
gMVP		0.33
Mutation Taster		=90/10	polymorphism

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: rs2282440; hg19: chr1-31347320;