chr11-2411734-T-C

Variant names:

• chr11-2411734-T-C
• rs2074234
• NM_014555.4:c.2508A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014555.4(TRPM5):​c.2508A>G​(p.Thr836Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,612,378 control chromosomes in the GnomAD database, including 100,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8702 hom., cov: 33)
  • Exomes 𝑓: 0.35 (91359 hom.)
• Consequence: TRPM5 NM_014555.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -7.71
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-7.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.43 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	NM_014555.4	MANE Select	c.2508A>G	p.Thr836Thr	synonymous	Exon 22 of 29	NP_055370.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM5	ENST00000696290.1	MANE Select	c.2508A>G	p.Thr836Thr	synonymous	Exon 22 of 29	ENSP00000512529.1
	TRPM5	ENST00000533060.5	TSL:1	c.2508A>G	p.Thr836Thr	synonymous	Exon 17 of 24	ENSP00000434121.1
	TRPM5	ENST00000528453.1	TSL:1	c.2508A>G	p.Thr836Thr	synonymous	Exon 17 of 24	ENSP00000436809.1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50163 AN: 151904 Hom.: 8698 Cov.: 33

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.375

GnomAD2 exomes AF: 0.362 AC: 90490 AN: 249662 AF XY: 0.362

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.463

Gnomad ASJ exome AF: 0.360

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.356

Gnomad OTH exome AF: 0.375

GnomAD4 exome AF: 0.351 AC: 512547 AN: 1460356 Hom.: 91359 Cov.: 59 AF XY: 0.351 AC XY: 254659 AN XY: 726474

African (AFR) AF: 0.235 AC: 7856 AN: 33472

American (AMR) AF: 0.452 AC: 20203 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9334 AN: 26124

East Asian (EAS) AF: 0.442 AC: 17538 AN: 39692

South Asian (SAS) AF: 0.338 AC: 29112 AN: 86254

European-Finnish (FIN) AF: 0.316 AC: 16473 AN: 52166

Middle Eastern (MID) AF: 0.425 AC: 2450 AN: 5766

European-Non Finnish (NFE) AF: 0.349 AC: 388051 AN: 1111816

Other (OTH) AF: 0.357 AC: 21530 AN: 60362

GnomAD4 genome AF: 0.330 AC: 50189 AN: 152022 Hom.: 8702 Cov.: 33 AF XY: 0.333 AC XY: 24781 AN XY: 74312

African (AFR) AF: 0.238 AC: 9860 AN: 41490

American (AMR) AF: 0.439 AC: 6703 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2204 AN: 5138

South Asian (SAS) AF: 0.326 AC: 1575 AN: 4824

European-Finnish (FIN) AF: 0.318 AC: 3362 AN: 10574

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24141 AN: 67926

Other (OTH) AF: 0.377 AC: 796 AN: 2112

Alfa AF: 0.354 Hom.: 19546

Bravo AF: 0.334

Asia WGS AF: 0.357 AC: 1241 AN: 3478

EpiCase AF: 0.367

EpiControl AF: 0.372

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.61
PhyloP100		-7.7
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: rs2074234; hg19: chr11-2432964; COSMIC: COSV50145665; COSMIC: COSV50145665;