20-45348372-G-C

Variant names:

• chr20-45348372-G-C
• rs1366052948
• NM_002999.4:c.13C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002999.4(SDC4):​c.13C>G​(p.Arg5Gly) 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. R5C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SDC4 NM_002999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14236742).

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>G	p.Arg5Gly	missense	Exon 1 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.13C>G	p.Arg5Gly	missense	Exon 1 of 5	ENSP00000361818.3	P31431-1
	SDC4	ENST00000901705.1		c.13C>G	p.Arg5Gly	missense	Exon 1 of 5	ENSP00000571764.1
	SDC4	ENST00000939835.1		c.13C>G	p.Arg5Gly	missense	Exon 1 of 5	ENSP00000609894.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.010
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.035
Sift	Benign	0.048	D
Sift4G	Benign	0.44	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.41		Loss of methylation at A5 (P = 0.0071)
MVP		0.31
MPC		0.15
ClinPred		0.081	T
GERP RS		0.43
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.14
gMVP		0.31
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1366052948; hg19: chr20-43977012;