11-2418537-T-C

Variant names:

• chr11-2418537-T-C
• rs886277
• NM_014555.4:c.704A>G

Variant summary

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

The NM_014555.4(TRPM5):​c.704A>G​(p.Asn235Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 1,609,256 control chromosomes in the GnomAD database, including 144,792 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.47 (17434 hom., cov: 31)
  • Exomes 𝑓: 0.41 (127358 hom.)
• Consequence: TRPM5 NM_014555.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 49 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=5.790589E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 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.704A>G	p.Asn235Ser	missense	Exon 10 of 29	NP_055370.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	ENST00000696290.1	MANE Select	c.704A>G	p.Asn235Ser	missense	Exon 10 of 29	ENSP00000512529.1
	TRPM5	ENST00000533060.5	TSL:1	c.704A>G	p.Asn235Ser	missense	Exon 5 of 24	ENSP00000434121.1
	TRPM5	ENST00000528453.1	TSL:1	c.704A>G	p.Asn235Ser	missense	Exon 5 of 24	ENSP00000436809.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70824 AN: 151542 Hom.: 17408 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.438

GnomAD2 exomes AF: 0.443 AC: 107787 AN: 243486 AF XY: 0.433

Gnomad AFR exome AF: 0.613

Gnomad AMR exome AF: 0.513

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.674

Gnomad FIN exome AF: 0.419

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.417

GnomAD4 exome AF: 0.413 AC: 601553 AN: 1457596 Hom.: 127358 Cov.: 48 AF XY: 0.411 AC XY: 298119 AN XY: 724842

African (AFR) AF: 0.610 AC: 20397 AN: 33416

American (AMR) AF: 0.511 AC: 22621 AN: 44284

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6817 AN: 26070

East Asian (EAS) AF: 0.700 AC: 27723 AN: 39580

South Asian (SAS) AF: 0.417 AC: 35801 AN: 85760

European-Finnish (FIN) AF: 0.426 AC: 22123 AN: 51922

Middle Eastern (MID) AF: 0.372 AC: 2140 AN: 5760

European-Non Finnish (NFE) AF: 0.395 AC: 438657 AN: 1110558

Other (OTH) AF: 0.420 AC: 25274 AN: 60246

GnomAD4 genome AF: 0.467 AC: 70893 AN: 151660 Hom.: 17434 Cov.: 31 AF XY: 0.464 AC XY: 34395 AN XY: 74086

African (AFR) AF: 0.606 AC: 25049 AN: 41346

American (AMR) AF: 0.453 AC: 6910 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3462

East Asian (EAS) AF: 0.671 AC: 3411 AN: 5086

South Asian (SAS) AF: 0.445 AC: 2133 AN: 4796

European-Finnish (FIN) AF: 0.421 AC: 4408 AN: 10482

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26755 AN: 67922

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.419 Hom.: 57557

Bravo AF: 0.479

TwinsUK AF: 0.369 AC: 1368

ALSPAC AF: 0.396 AC: 1526

ESP6500AA AF: 0.613 AC: 2693

ESP6500EA AF: 0.385 AC: 3312

ExAC AF: 0.442 AC: 53329

Asia WGS AF: 0.540 AC: 1876 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.1
DANN	Benign	0.19
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0000058	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.67	N
PhyloP100		0.24
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.062
Sift	Benign	0.74	T
Sift4G	Benign	0.83	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.071
ClinPred		0.0029	T
GERP RS		1.4
Varity_R		0.038
gMVP		0.24
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: rs886277; hg19: chr11-2439767; COSMIC: COSV50148399;