chr13-37637415-C-T

Variant names:

• chr13-37637415-C-T
• NM_016179.4:c.2422G>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.2422G>A​(p.Ala808Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRPC4 NM_016179.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93
• Publications: 0 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=0.16608864).

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.2422G>A	p.Ala808Thr	missense	Exon 11 of 11	NP_057263.1	Q9UBN4-1
	TRPC4	NM_003306.3		c.2437G>A	p.Ala813Thr	missense	Exon 11 of 11	NP_003297.1	Q9UBN4-5
	TRPC4	NM_001135958.3		c.1903G>A	p.Ala635Thr	missense	Exon 10 of 10	NP_001129430.1	Q9UBN4-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPC4	ENST00000379705.8	TSL:1 MANE Select	c.2422G>A	p.Ala808Thr	missense	Exon 11 of 11	ENSP00000369027.4	Q9UBN4-1
	TRPC4	ENST00000625583.2	TSL:1	c.2437G>A	p.Ala813Thr	missense	Exon 10 of 10	ENSP00000486109.1	Q9UBN4-5
	TRPC4	ENST00000379679.5	TSL:1	c.1903G>A	p.Ala635Thr	missense	Exon 9 of 9	ENSP00000369001.1	Q9UBN4-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461518 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111820

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

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	0.097
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.052
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.16
Sift	Benign	0.097	T
Sift4G	Benign	0.46	T
Polyphen		0.0080	B
Vest4		0.40
MutPred		0.26		Gain of glycosylation at A808 (P = 0.0362)
MVP		0.36
ClinPred		0.52	D
GERP RS		5.9
Varity_R		0.039
gMVP		0.56
Mutation Taster		=59/41	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

hg19: chr13-38211552;