11-2407187-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014555.4(TRPM5):ā€‹c.3050T>Cā€‹(p.Leu1017Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

TRPM5
NM_014555.4 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.75
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.896

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPM5NM_014555.4 linkuse as main transcriptc.3050T>C p.Leu1017Pro missense_variant 25/29 ENST00000696290.1
TRPM5XM_017017628.2 linkuse as main transcriptc.3104T>C p.Leu1035Pro missense_variant 22/26
TRPM5XM_047426858.1 linkuse as main transcriptc.3104T>C p.Leu1035Pro missense_variant 22/26
TRPM5XM_047426859.1 linkuse as main transcriptc.1901T>C p.Leu634Pro missense_variant 13/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPM5ENST00000696290.1 linkuse as main transcriptc.3050T>C p.Leu1017Pro missense_variant 25/29 NM_014555.4 P2Q9NZQ8-1
ENST00000433035.1 linkuse as main transcriptn.320-637A>G intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
245328
Hom.:
0
AF XY:
0.0000225
AC XY:
3
AN XY:
133590
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000271
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1459086
Hom.:
0
Cov.:
36
AF XY:
0.00000413
AC XY:
3
AN XY:
725872
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152176
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000248
AC:
3

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 submitterclinical testingAmbry GeneticsJan 24, 2024The c.3050T>C (p.L1017P) alteration is located in exon 20 (coding exon 20) of the TRPM5 gene. This alteration results from a T to C substitution at nucleotide position 3050, causing the leucine (L) at amino acid position 1017 to be replaced by a proline (P). 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
0.23
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.67
.;D;.;.
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Uncertain
0.25
D
MetaRNN
Pathogenic
0.90
D;D;D;D
MetaSVM
Benign
-0.28
T
MutationAssessor
Uncertain
2.4
.;M;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-5.4
D;D;D;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0030
D;D;D;D
Polyphen
0.68, 0.82
.;P;P;.
Vest4
0.93, 0.88, 0.93
MutPred
0.76
.;Loss of stability (P = 0.0828);Loss of stability (P = 0.0828);Loss of stability (P = 0.0828);
MVP
0.57
MPC
0.15
ClinPred
0.98
D
GERP RS
3.2
Varity_R
0.90
gMVP
0.85

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.

Other links and lift over

dbSNP: rs750199656; hg19: chr11-2428417; API