rs1951539968

Variant names:

• chr13-37636928-T-C
• rs1951539968
• NM_016179.4:c.2909A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-37636928-T-C
• chr13-37636928-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016179.4(TRPC4):​c.2909A>G​(p.Glu970Gly) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPC4 NM_016179.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

Genes affected

TRPC4 (HGNC:12336): (transient receptor potential cation channel subfamily C member 4) This gene encodes a member of the canonical subfamily of transient receptor potential cation channels. The encoded protein forms a non-selective calcium-permeable cation channel that is activated by Gq-coupled receptors and tyrosine kinases, and plays a role in multiple processes including endothelial permeability, vasodilation, neurotransmitter release and cell proliferation. Single nucleotide polymorphisms in this gene may be associated with generalized epilepsy with photosensitivity. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07183859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPC4	NM_016179.4	c.2909A>G	p.Glu970Gly	missense_variant	Exon 11 of 11	ENST00000379705.8	NP_057263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPC4	ENST00000379705.8	c.2909A>G	p.Glu970Gly	missense_variant	Exon 11 of 11	1	NM_016179.4	ENSP00000369027.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.26	T;.;.;.;.;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.78	T;T;T;.;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.072	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.34	N;.;.;.;.;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N;N;.;N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.24	T;T;.;T;T;D;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B;B
Vest4		0.089
MutPred		0.26		Loss of solvent accessibility (P = 0.0477);.;.;.;.;.;.;
MVP		0.32
ClinPred		0.10	T
GERP RS		4.3
Varity_R		0.051
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs1951539968; hg19: chr13-38211065;