Genetic Variant TRPM5:p.Thr836Thr (chr11-2411734-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -7.71

Publications

19 publications found

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]

TRPM5 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM5	NM_014555.4 link	c.2508A>G	p.Thr836Thr	synonymous_variant	Exon 22 of 29	ENST00000696290.1	NP_055370.1	Q9NZQ8-1
TRPM5	XM_017017628.2 link	c.2562A>G	p.Thr854Thr	synonymous_variant	Exon 19 of 26		XP_016873117.1
TRPM5	XM_047426858.1 link	c.2562A>G	p.Thr854Thr	synonymous_variant	Exon 19 of 26		XP_047282814.1
TRPM5	XM_047426859.1 link	c.1359A>G	p.Thr453Thr	synonymous_variant	Exon 10 of 17		XP_047282815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPM5	ENST00000696290.1 link	c.2508A>G	p.Thr836Thr	synonymous_variant	Exon 22 of 29		NM_014555.4	ENSP00000512529.1	Q9NZQ8-1
TRPM5	ENST00000533060.5 link	c.2508A>G	p.Thr836Thr	synonymous_variant	Exon 17 of 24	1		ENSP00000434121.1	E9PRW0
TRPM5	ENST00000528453.1 link	c.2508A>G	p.Thr836Thr	synonymous_variant	Exon 17 of 24	1		ENSP00000436809.1	E9PQF7
TRPM5	ENST00000533881.5 link	c.2490A>G	p.Thr830Thr	synonymous_variant	Exon 17 of 24	1		ENSP00000434383.1	A0A0C4DGF4

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50163

AN:

151904

Hom.:

8698

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.351

AC XY:

254659

AN XY:

726474

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20102

40205

60307

80410

100512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12412

24824

37236

49648

62060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.330

AC:

50189

AN:

152022

Hom.:

8702

Cov.:

AF XY:

0.333

AC XY:

24781

AN XY:

74312

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1720

3440

5159

6879

8599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.14

(source)

DANN

Benign

0.61

PhyloP100

-7.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over