chr11-2406676-C-T

Position:

chr11-2406676-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014555.4(TRPM5):c.3236G>A(p.Arg1079Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000391 in 1,611,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

TRPM5
NM_014555.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.188

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:

ENSG00000230483 (HGNC:):

ENSG00000230483 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.118939996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM5	NM_014555.4 link	c.3236G>A	p.Arg1079Gln	missense_variant	26/29	ENST00000696290.1	NP_055370.1	Q9NZQ8-1
TRPM5	XM_017017628.2 link	c.3290G>A	p.Arg1097Gln	missense_variant	23/26		XP_016873117.1
TRPM5	XM_047426858.1 link	c.3290G>A	p.Arg1097Gln	missense_variant	23/26		XP_047282814.1
TRPM5	XM_047426859.1 link	c.2087G>A	p.Arg696Gln	missense_variant	14/17		XP_047282815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM5	ENST00000696290.1 link	c.3236G>A	p.Arg1079Gln	missense_variant	26/29		NM_014555.4	ENSP00000512529.1		Q9NZQ8-1

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

249232

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

134770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000929

Gnomad NFE exome

AF:

0.0000712

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1459204

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

725842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000897

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000570

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000756

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.3236G>A (p.R1079Q) alteration is located in exon 21 (coding exon 21) of the TRPM5 gene. This alteration results from a G to A substitution at nucleotide position 3236, causing the arginine (R) at amino acid position 1079 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

.;T;.;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.85

D;D;T;D

M_CAP

Uncertain

0.098

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.6

.;L;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.58

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.35

T;T;T;T

Sift4G

Uncertain

0.021

D;D;D;D

Polyphen

0.99

.;D;D;.

Vest4

0.25, 0.26, 0.24

MVP

0.14

MPC

0.12

ClinPred

0.59

GERP RS

2.0

Varity_R

0.074

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over