11-2418312-A-T

Variant names:

• chr11-2418312-A-T
• rs3986599
• NM_014555.4:c.761T>A

Variant summary

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

The NM_014555.4(TRPM5):​c.761T>A​(p.Val254Glu) 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRPM5 NM_014555.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.93
• Publications: 23 publications found

Genes affected

TRPM5 (HGNC:14323): (transient receptor potential cation channel subfamily M member 5) This gene encodes a member of the transient receptor potential (TRP) protein family, which is a diverse group of proteins with structural features typical of ion channels. This protein plays an important role in taste transduction, and has characteristics of a calcium-activated, non-selective cation channel that carries Na+, K+, and Cs+ ions equally well, but not Ca(2+) ions. It is activated by lower concentrations of intracellular Ca(2+), and inhibited by higher concentrations. It is also a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. This gene is located within the Beckwith-Wiedemann syndrome critical region-1 on chromosome 11p15.5, and has been shown to be imprinted, with exclusive expression from the paternal allele. [provided by RefSeq, Oct 2010]

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=0.1232124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM5	NM_014555.4	c.761T>A	p.Val254Glu	missense_variant	Exon 11 of 29	ENST00000696290.1	NP_055370.1
TRPM5	XM_017017628.2	c.815T>A	p.Val272Glu	missense_variant	Exon 8 of 26		XP_016873117.1
TRPM5	XM_047426858.1	c.815T>A	p.Val272Glu	missense_variant	Exon 8 of 26		XP_047282814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM5	ENST00000696290.1	c.761T>A	p.Val254Glu	missense_variant	Exon 11 of 29		NM_014555.4	ENSP00000512529.1
TRPM5	ENST00000533060.5	c.761T>A	p.Val254Glu	missense_variant	Exon 6 of 24	1		ENSP00000434121.1
TRPM5	ENST00000528453.1	c.761T>A	p.Val254Glu	missense_variant	Exon 6 of 24	1		ENSP00000436809.1
TRPM5	ENST00000533881.5	c.743T>A	p.Val248Glu	missense_variant	Exon 6 of 24	1		ENSP00000434383.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1417082 Hom.: 0 Cov.: 71 AF XY: 0.00 AC XY: 0 AN XY: 700646

African (AFR) AF: 0.00 AC: 0 AN: 32470

American (AMR) AF: 0.00 AC: 0 AN: 38186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25398

East Asian (EAS) AF: 0.00 AC: 0 AN: 37290

South Asian (SAS) AF: 0.00 AC: 0 AN: 81058

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5706

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089532

Other (OTH) AF: 0.00 AC: 0 AN: 58626

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.12	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.080	T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	.;N;.;.
PhyloP100		2.9
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.6	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.44	T;T;T;T
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.062, 0.0020	.;B;B;.
Vest4		0.19, 0.26, 0.19
MutPred		0.57		.;Loss of stability (P = 0.126);Loss of stability (P = 0.126);Loss of stability (P = 0.126);
MVP		0.014
MPC		0.15
ClinPred		0.43	T
GERP RS		2.5
Varity_R		0.11
gMVP		0.57
Mutation Taster		=94/6	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: rs3986599; hg19: chr11-2439542;