20-45327377-C-A

Variant names:

• chr20-45327377-C-A
• rs202142981
• NM_002999.4:c.484G>T

Variant summary

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

The NM_002999.4(SDC4):​c.484G>T​(p.Val162Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 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. V162I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SDC4 NM_002999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.484G>T	p.Val162Phe	missense	Exon 5 of 5	NP_002990.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDC4	ENST00000372733.3	TSL:1 MANE Select	c.484G>T	p.Val162Phe	missense	Exon 5 of 5	ENSP00000361818.3	P31431-1
	SDC4	ENST00000901705.1		c.493G>T	p.Val165Phe	missense	Exon 5 of 5	ENSP00000571764.1
	SDC4	ENST00000939835.1		c.463G>T	p.Val155Phe	missense	Exon 5 of 5	ENSP00000609894.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	D
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.8	L
PhyloP100		-0.76
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.50		Loss of stability (P = 0.0529)
MVP		0.42
MPC		0.63
ClinPred		0.97	D
GERP RS		-3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.36
gMVP		0.80
Mutation Taster		=73/27	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: rs202142981; hg19: chr20-43956017;