dbSNP rs774614953: SDC1:p.Val262Leu (chr2-20202915-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002997.5(SDC1):c.784G>T(p.Val262Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V262M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDC1
NM_002997.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

SDC1 (HGNC:10658): (syndecan 1) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein. [provided by RefSeq, Jul 2008]

SDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDC1	NM_002997.5 link	c.784G>T	p.Val262Leu	missense_variant	Exon 5 of 5	ENST00000254351.9	NP_002988.4	P18827

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDC1	ENST00000254351.9 link	c.784G>T	p.Val262Leu	missense_variant	Exon 5 of 5	1	NM_002997.5	ENSP00000254351.4	P18827
SDC1	ENST00000403076.5 link	c.479-614G>T		intron_variant	Intron 3 of 3	1		ENSP00000384613.1	E9PHH3
SDC1	ENST00000381150.5 link	c.784G>T	p.Val262Leu	missense_variant	Exon 6 of 6	5		ENSP00000370542.1	P18827

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459934

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;D

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.9

L;L

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

D;D

REVEL

Uncertain

0.31

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

0.94

P;P

Vest4

0.55

MutPred

0.80

Loss of sheet (P = 0.3635);Loss of sheet (P = 0.3635);

MVP

0.42

MPC

0.83

ClinPred

0.94

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.85

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over