11-2415234-C-A

Variant names:

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:

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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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM5	NM_014555.4 link	c.1366G>T	p.Ala456Ser	missense_variant	Exon 14 of 29	ENST00000696290.1	NP_055370.1	Q9NZQ8-1
TRPM5	XM_017017628.2 link	c.1420G>T	p.Ala474Ser	missense_variant	Exon 11 of 26		XP_016873117.1
TRPM5	XM_047426858.1 link	c.1420G>T	p.Ala474Ser	missense_variant	Exon 11 of 26		XP_047282814.1
TRPM5	XM_047426859.1 link	c.217G>T	p.Ala73Ser	missense_variant	Exon 2 of 17		XP_047282815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPM5	ENST00000696290.1 link	c.1366G>T	p.Ala456Ser	missense_variant	Exon 14 of 29		NM_014555.4	ENSP00000512529.1	Q9NZQ8-1
TRPM5	ENST00000533060.5 link	c.1366G>T	p.Ala456Ser	missense_variant	Exon 9 of 24	1		ENSP00000434121.1	E9PRW0
TRPM5	ENST00000528453.1 link	c.1366G>T	p.Ala456Ser	missense_variant	Exon 9 of 24	1		ENSP00000436809.1	E9PQF7
TRPM5	ENST00000533881.5 link	c.1348G>T	p.Ala450Ser	missense_variant	Exon 9 of 24	1		ENSP00000434383.1	A0A0C4DGF4

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 v4.3

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

.;T;.;.

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.22

T;T;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.031

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.47

.;N;.;.

PhyloP100

-2.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.51

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.80

T;T;T;T

Sift4G

Benign

0.75

T;T;T;T

Polyphen

0.016, 0.0040

.;B;B;.

Vest4

0.058, 0.067, 0.083

MutPred

0.30

.;Gain of relative solvent accessibility (P = 0.0024);Gain of relative solvent accessibility (P = 0.0024);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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over