1-30874395-C-G

Variant names:

• chr1-30874395-C-G
• rs201560193
• NM_014654.4:c.1064G>C

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.1064G>C​(p.Arg355Pro) 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. R355L) 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: 0.564
• Publications: 1 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=0.11978692).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014654.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC3	NM_014654.4	MANE Select	c.1064G>C	p.Arg355Pro	missense	Exon 4 of 5	NP_055469.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC3	ENST00000339394.7	TSL:1 MANE Select	c.1064G>C	p.Arg355Pro	missense	Exon 4 of 5	ENSP00000344468.6	O75056
	SDC3	ENST00000336798.11	TSL:1	c.890G>C	p.Arg297Pro	missense	Exon 2 of 3	ENSP00000338346.7	A0A9K3Y886
	SDC3	ENST00000937355.1		c.1016G>C	p.Arg339Pro	missense	Exon 4 of 5	ENSP00000607414.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000152 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.56
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.066
Sift	Uncertain	0.025	D
Sift4G	Benign	0.19	T
Polyphen		0.30	B
Vest4		0.21
MutPred		0.40		Gain of glycosylation at R355 (P = 0.0237)
MVP		0.093
MPC		0.096
ClinPred		0.22	T
GERP RS		1.8
Varity_R		0.16
gMVP		0.34
Mutation Taster		=81/19	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: rs201560193; hg19: chr1-31347242;