Genetic Variant TRPM5:p.Val254Glu (chr11-2418312-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93

Publications

23 publications found

Variant links:

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]

TRPM5 links:

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ACMG classification

Classification was made for transcript

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014555.4. 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
	TRPM5	NM_014555.4	MANE Select	c.761T>A	p.Val254Glu	missense	Exon 11 of 29	NP_055370.1	Q9NZQ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TRPM5	ENST00000696290.1	MANE Select	c.761T>A	p.Val254Glu	missense	Exon 11 of 29	ENSP00000512529.1	Q9NZQ8-1
TRPM5	ENST00000533060.5	TSL:1	c.761T>A	p.Val254Glu	missense	Exon 6 of 24	ENSP00000434121.1	E9PRW0
TRPM5	ENST00000528453.1	TSL:1	c.761T>A	p.Val254Glu	missense	Exon 6 of 24	ENSP00000436809.1	E9PQF7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417082

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

700646

African (AFR)

AF:

0.00

AC:

AN:

32470

American (AMR)

AF:

0.00

AC:

AN:

38186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

37290

South Asian (SAS)

AF:

0.00

AC:

AN:

81058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089532

Other (OTH)

AF:

0.00

AC:

AN:

58626

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.080

M_CAP

Benign

0.0065

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.4

PhyloP100

2.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

1.6

REVEL

Benign

0.13

Sift

Benign

0.44

Sift4G

Uncertain

0.0020

Polyphen

0.062

Vest4

0.19

MutPred

0.57

Loss of stability (P = 0.126)

MVP

0.014

MPC

0.15

ClinPred

0.43

GERP RS

2.5

Varity_R

0.11

gMVP

0.57

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over