Genetic Variant SDC4:p.Gly52Trp (chr20-45335827-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002999.4(SDC4):c.154G>T(p.Gly52Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G52R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SDC4
NM_002999.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Publications

0 publications found

Variant links:

Genes affected

SDC4 (HGNC:10661): (syndecan 4) The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan that functions as a receptor in intracellular signaling. The encoded protein is found as a homodimer and is a member of the syndecan proteoglycan family. This gene is found on chromosome 20, while a pseudogene has been found on chromosome 22. [provided by RefSeq, Jul 2008]

SDC4 links:

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ACMG classification

Classification was made for transcript

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=0.13265613).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002999.4. 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
	SDC4	NM_002999.4	MANE Select	c.154G>T	p.Gly52Trp	missense	Exon 2 of 5	NP_002990.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SDC4	ENST00000372733.3	TSL:1 MANE Select	c.154G>T	p.Gly52Trp	missense	Exon 2 of 5	ENSP00000361818.3	P31431-1
SDC4	ENST00000901705.1		c.154G>T	p.Gly52Trp	missense	Exon 2 of 5	ENSP00000571764.1
SDC4	ENST00000939835.1		c.133G>T	p.Gly45Trp	missense	Exon 2 of 5	ENSP00000609894.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.38

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.58

M_CAP

Benign

0.016

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

PhyloP100

1.7

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

REVEL

Benign

0.033

Sift

Benign

0.19

Sift4G

Benign

0.19

Polyphen

0.010

Vest4

0.32

MutPred

0.30

Loss of relative solvent accessibility (P = 0.0404)

MVP

0.31

MPC

0.61

ClinPred

0.50

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.31

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over