rs3986599

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014555.4(TRPM5):ā€‹c.761T>Cā€‹(p.Val254Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,568,652 control chromosomes in the GnomAD database, including 376,855 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: š‘“ 0.76 ( 44998 hom., cov: 31)
Exomes š‘“: 0.68 ( 331857 hom. )

Consequence

TRPM5
NM_014555.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.93
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=2.197801E-6).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TRPM5NM_014555.4 linkuse as main transcriptc.761T>C p.Val254Ala missense_variant 11/29 ENST00000696290.1 NP_055370.1
TRPM5XM_017017628.2 linkuse as main transcriptc.815T>C p.Val272Ala missense_variant 8/26 XP_016873117.1
TRPM5XM_047426858.1 linkuse as main transcriptc.815T>C p.Val272Ala missense_variant 8/26 XP_047282814.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRPM5ENST00000696290.1 linkuse as main transcriptc.761T>C p.Val254Ala missense_variant 11/29 NM_014555.4 ENSP00000512529 P2Q9NZQ8-1
TRPM5ENST00000533060.5 linkuse as main transcriptc.761T>C p.Val254Ala missense_variant 6/241 ENSP00000434121 A2
TRPM5ENST00000528453.1 linkuse as main transcriptc.761T>C p.Val254Ala missense_variant 6/241 ENSP00000436809 A2
TRPM5ENST00000533881.5 linkuse as main transcriptc.743T>C p.Val248Ala missense_variant 6/241 ENSP00000434383

Frequencies

GnomAD3 genomes
AF:
0.760
AC:
115289
AN:
151730
Hom.:
44939
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.929
Gnomad AMI
AF:
0.489
Gnomad AMR
AF:
0.812
Gnomad ASJ
AF:
0.657
Gnomad EAS
AF:
0.898
Gnomad SAS
AF:
0.787
Gnomad FIN
AF:
0.656
Gnomad MID
AF:
0.744
Gnomad NFE
AF:
0.658
Gnomad OTH
AF:
0.768
GnomAD3 exomes
AF:
0.738
AC:
133451
AN:
180908
Hom.:
50177
AF XY:
0.732
AC XY:
71237
AN XY:
97342
show subpopulations
Gnomad AFR exome
AF:
0.937
Gnomad AMR exome
AF:
0.858
Gnomad ASJ exome
AF:
0.659
Gnomad EAS exome
AF:
0.896
Gnomad SAS exome
AF:
0.773
Gnomad FIN exome
AF:
0.649
Gnomad NFE exome
AF:
0.656
Gnomad OTH exome
AF:
0.723
GnomAD4 exome
AF:
0.681
AC:
964449
AN:
1416804
Hom.:
331857
Cov.:
71
AF XY:
0.682
AC XY:
477741
AN XY:
700460
show subpopulations
Gnomad4 AFR exome
AF:
0.940
Gnomad4 AMR exome
AF:
0.853
Gnomad4 ASJ exome
AF:
0.657
Gnomad4 EAS exome
AF:
0.892
Gnomad4 SAS exome
AF:
0.771
Gnomad4 FIN exome
AF:
0.653
Gnomad4 NFE exome
AF:
0.653
Gnomad4 OTH exome
AF:
0.708
GnomAD4 genome
AF:
0.760
AC:
115408
AN:
151848
Hom.:
44998
Cov.:
31
AF XY:
0.761
AC XY:
56460
AN XY:
74174
show subpopulations
Gnomad4 AFR
AF:
0.929
Gnomad4 AMR
AF:
0.813
Gnomad4 ASJ
AF:
0.657
Gnomad4 EAS
AF:
0.898
Gnomad4 SAS
AF:
0.786
Gnomad4 FIN
AF:
0.656
Gnomad4 NFE
AF:
0.658
Gnomad4 OTH
AF:
0.767
Alfa
AF:
0.686
Hom.:
41256
Bravo
AF:
0.780
TwinsUK
AF:
0.634
AC:
2352
ALSPAC
AF:
0.660
AC:
2542
ESP6500AA
AF:
0.924
AC:
4013
ESP6500EA
AF:
0.663
AC:
5658
ExAC
AF:
0.694
AC:
78778
Asia WGS
AF:
0.835
AC:
2906
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.041
BayesDel_addAF
Benign
-0.77
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
15
DANN
Benign
0.14
DEOGEN2
Benign
0.12
.;T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.015
T;T;T;T
MetaRNN
Benign
0.0000022
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-2.6
.;N;.;.
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
2.5
N;N;N;N
REVEL
Benign
0.12
Sift
Benign
1.0
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.0
.;B;B;.
Vest4
0.049, 0.027, 0.046
MPC
0.11
ClinPred
0.0017
T
GERP RS
2.5
Varity_R
0.034
gMVP
0.36

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.

Other links and lift over

dbSNP: rs3986599; hg19: chr11-2439542; COSMIC: COSV50155045; API