13-37637169-C-T

Variant names:

• chr13-37637169-C-T
• rs147399086
• NM_016179.4:c.2668G>A

Variant summary

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

The NM_016179.4(TRPC4):​c.2668G>A​(p.Gly890Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TRPC4 NM_016179.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 1 publications found

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]

ENSG00000297050 (HGNC:):

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=0.088487804).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016179.4. 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
	TRPC4	NM_016179.4	MANE Select	c.2668G>A	p.Gly890Arg	missense	Exon 11 of 11	NP_057263.1	Q9UBN4-1
	TRPC4	NM_003306.3		c.2683G>A	p.Gly895Arg	missense	Exon 11 of 11	NP_003297.1	Q9UBN4-5
	TRPC4	NM_001135955.3		c.2416G>A	p.Gly806Arg	missense	Exon 12 of 12	NP_001129427.1	Q9UBN4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4	ENST00000379705.8	TSL:1 MANE Select	c.2668G>A	p.Gly890Arg	missense	Exon 11 of 11	ENSP00000369027.4	Q9UBN4-1
	TRPC4	ENST00000625583.2	TSL:1	c.2683G>A	p.Gly895Arg	missense	Exon 10 of 10	ENSP00000486109.1	Q9UBN4-5
	TRPC4	ENST00000358477.6	TSL:1	c.2416G>A	p.Gly806Arg	missense	Exon 12 of 12	ENSP00000351264.2	Q9UBN4-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74302

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.068
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.52	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.28		Gain of MoRF binding (P = 0.0123)
MVP		0.27
ClinPred		0.32	T
GERP RS		4.5
Varity_R		0.083
gMVP		0.31
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: rs147399086; hg19: chr13-38211306;