11-2405530-G-A

Position:

chr11-2405530-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014555.4(TRPM5):c.3388C>T(p.Arg1130Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,558,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

TRPM5
NM_014555.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.47

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01251775).

BP6

Variant 11-2405530-G-A is Benign according to our data. Variant chr11-2405530-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2266704.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TRPM5	NM_014555.4 linkuse as main transcript	c.3388C>T	p.Arg1130Trp	missense_variant	28/29	ENST00000696290.1
TRPM5	XM_017017628.2 linkuse as main transcript	c.3466C>T	p.Arg1156Trp	missense_variant	25/26
TRPM5	XM_047426858.1 linkuse as main transcript	c.3442C>T	p.Arg1148Trp	missense_variant	25/26
TRPM5	XM_047426859.1 linkuse as main transcript	c.2263C>T	p.Arg755Trp	missense_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM5	ENST00000696290.1 linkuse as main transcript	c.3388C>T	p.Arg1130Trp	missense_variant	28/29		NM_014555.4	P2	Q9NZQ8-1
	ENST00000433035.1 linkuse as main transcript	n.319+697G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000716

AC:

AN:

167592

Hom.:

AF XY:

0.0000338

AC XY:

AN XY:

88718

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.0000775

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000855

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000745

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

172

AN:

1406578

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

694510

show subpopulations

Gnomad4 AFR exome

AF:

0.000652

Gnomad4 AMR exome

AF:

0.0000545

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000627

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000126

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.000302

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.000796

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000931

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.0000523

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Benign

5.3

DANN

Benign

0.91

DEOGEN2

Benign

0.098

.;T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.34

T;T;T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

.;N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.030

N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.082

T;T;T;T

Sift4G

Benign

0.076

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.15, 0.15, 0.14

MVP

0.040

MPC

0.092

ClinPred

0.063

GERP RS

0.11

Varity_R

0.065

gMVP

0.14

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

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