dbSNP rs34551253: TRPM5:p.Ala456Ser (chr11-2415234-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014555.4(TRPM5):c.1366G>T(p.Ala456Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000563 in 1,420,670 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

TRPM5
NM_014555.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.030515373).

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.1366G>T	p.Ala456Ser	missense	Exon 14 of 29	NP_055370.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TRPM5	ENST00000696290.1	MANE Select	c.1366G>T	p.Ala456Ser	missense	Exon 14 of 29	ENSP00000512529.1
TRPM5	ENST00000533060.5	TSL:1	c.1366G>T	p.Ala456Ser	missense	Exon 9 of 24	ENSP00000434121.1
TRPM5	ENST00000528453.1	TSL:1	c.1366G>T	p.Ala456Ser	missense	Exon 9 of 24	ENSP00000436809.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

176620

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000563

AC:

AN:

1420670

Hom.:

Cov.:

AF XY:

0.00000994

AC XY:

AN XY:

704158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32730

American (AMR)

AF:

0.00

AC:

AN:

39904

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25460

East Asian (EAS)

AF:

0.00

AC:

AN:

37730

South Asian (SAS)

AF:

0.0000122

AC:

AN:

82102

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5666

European-Non Finnish (NFE)

AF:

0.00000548

AC:

AN:

1094554

Other (OTH)

AF:

0.0000170

AC:

AN:

58928

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0020

(source)

DANN

Benign

0.38

DEOGEN2

Benign

0.074

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.22

M_CAP

Benign

0.031

MetaRNN

Benign

0.031

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.47

PhyloP100

-2.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.51

REVEL

Benign

0.033

Sift

Benign

0.80

Sift4G

Benign

0.75

Polyphen

0.016

Vest4

0.058

MutPred

0.30

Gain of relative solvent accessibility (P = 0.0024)

MVP

0.014

MPC

0.082

ClinPred

0.046

GERP RS

-6.4

Varity_R

0.047

gMVP

0.17

Mutation Taster

=95/5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over