Genetic Variant NM_002999.4:c.13C>A (chr20-45348372-G-T) – 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.13C>A(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R5C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SDC4
NM_002999.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0100

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=0.15960044).

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.13C>A	p.Arg5Ser	missense	Exon 1 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.13C>A	p.Arg5Ser	missense	Exon 1 of 5	ENSP00000361818.3	P31431-1
SDC4	ENST00000901705.1		c.13C>A	p.Arg5Ser	missense	Exon 1 of 5	ENSP00000571764.1
SDC4	ENST00000939835.1		c.13C>A	p.Arg5Ser	missense	Exon 1 of 5	ENSP00000609894.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1434092

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32650

American (AMR)

AF:

0.00

AC:

AN:

41376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25386

East Asian (EAS)

AF:

0.00

AC:

AN:

37932

South Asian (SAS)

AF:

0.00

AC:

AN:

82616

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100140

Other (OTH)

AF:

0.00

AC:

AN:

59358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.15

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.47

M_CAP

Benign

0.063

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.010

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.16

REVEL

Benign

0.036

Sift

Benign

0.038

Sift4G

Benign

0.56

Polyphen

0.31

Vest4

0.21

MutPred

0.47

Loss of methylation at R5 (P = 0.0071)

MVP

0.34

MPC

0.14

ClinPred

0.11

GERP RS

0.43

PromoterAI

0.098

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.19

gMVP

0.34

Mutation Taster

=87/13

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over