chr13-37674318-G-T

Position:

• chr13-37674318-G-T

Variant summary

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

The NM_016179.4(TRPC4):​c.1284C>A​(p.Asp428Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRPC4 NM_016179.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.26

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=0.11224717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPC4	NM_016179.4	c.1284C>A	p.Asp428Glu	missense_variant	5/11	ENST00000379705.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPC4	ENST00000379705.8	c.1284C>A	p.Asp428Glu	missense_variant	5/11	1	NM_016179.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.1284C>A (p.D428E) alteration is located in exon 5 (coding exon 4) of the TRPC4 gene. This alteration results from a C to A substitution at nucleotide position 1284, causing the aspartic acid (D) at amino acid position 428 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Benign	0.44
DEOGEN2	Uncertain	0.44	T;.;.;.;.;.;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.86	D;D;D;.;D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.11	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	-0.59	N;.;N;.;.;N;N;N
MutationTaster	Benign	0.94	D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.49	N;N;.;N;N;N;N;N
REVEL	Uncertain	0.52
Sift	Benign	1.0	T;T;.;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;T
Polyphen		0.027	B;B;P;B;.;B;B;B
Vest4		0.16
MutPred		0.39		Gain of loop (P = 0.069);.;Gain of loop (P = 0.069);.;Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.61
ClinPred		0.14	T
GERP RS		2.6
Varity_R		0.068
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-38248455; COSMIC: COSV59011662;