11-2414726-C-T

Variant names:

• chr11-2414726-C-T
• rs4929982
• NM_014555.4:c.1733G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014555.4(TRPM5):​c.1733G>A​(p.Arg578Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,537,298 control chromosomes in the GnomAD database, including 178,538 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.48 (17594 hom., cov: 35)
  • Exomes 𝑓: 0.48 (160944 hom.)
• Consequence: TRPM5 NM_014555.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 22 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.4153857E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014555.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	NM_014555.4	MANE Select	c.1733G>A	p.Arg578Gln	missense	Exon 16 of 29	NP_055370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	ENST00000696290.1	MANE Select	c.1733G>A	p.Arg578Gln	missense	Exon 16 of 29	ENSP00000512529.1
	TRPM5	ENST00000533060.5	TSL:1	c.1733G>A	p.Arg578Gln	missense	Exon 11 of 24	ENSP00000434121.1
	TRPM5	ENST00000528453.1	TSL:1	c.1733G>A	p.Arg578Gln	missense	Exon 11 of 24	ENSP00000436809.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72584 AN: 151710 Hom.: 17568 Cov.: 35

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.470

GnomAD2 exomes AF: 0.492 AC: 69284 AN: 140736 AF XY: 0.488

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.539

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.679

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.471

Gnomad OTH exome AF: 0.482

GnomAD4 exome AF: 0.479 AC: 663889 AN: 1385470 Hom.: 160944 Cov.: 67 AF XY: 0.479 AC XY: 326557 AN XY: 682268

African (AFR) AF: 0.490 AC: 15329 AN: 31284

American (AMR) AF: 0.539 AC: 18917 AN: 35092

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8568 AN: 24922

East Asian (EAS) AF: 0.707 AC: 25065 AN: 35464

South Asian (SAS) AF: 0.474 AC: 37305 AN: 78724

European-Finnish (FIN) AF: 0.466 AC: 20717 AN: 44498

Middle Eastern (MID) AF: 0.435 AC: 2079 AN: 4776

European-Non Finnish (NFE) AF: 0.474 AC: 508619 AN: 1073356

Other (OTH) AF: 0.476 AC: 27290 AN: 57354

GnomAD4 genome AF: 0.479 AC: 72661 AN: 151828 Hom.: 17594 Cov.: 35 AF XY: 0.475 AC XY: 35230 AN XY: 74180

African (AFR) AF: 0.485 AC: 20125 AN: 41462

American (AMR) AF: 0.492 AC: 7515 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1137 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3388 AN: 5080

South Asian (SAS) AF: 0.494 AC: 2384 AN: 4824

European-Finnish (FIN) AF: 0.452 AC: 4778 AN: 10572

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31908 AN: 67840

Other (OTH) AF: 0.470 AC: 995 AN: 2116

Alfa AF: 0.472 Hom.: 9095

Bravo AF: 0.485

TwinsUK AF: 0.442 AC: 1640

ALSPAC AF: 0.480 AC: 1848

ESP6500AA AF: 0.451 AC: 1688

ESP6500EA AF: 0.421 AC: 3146

ExAC AF: 0.361 AC: 24651

Asia WGS AF: 0.556 AC: 1932 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.079	T
MetaRNN	Benign	0.0000054	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-2.1	N
PhyloP100		3.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.13
MPC		0.10
ClinPred		0.042	T
GERP RS		3.8
Varity_R		0.075
gMVP		0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4929982; hg19: chr11-2435956; COSMIC: COSV50144262;