rs4929982

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-2414726-C-A
• chr11-2414726-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014555.4(TRPM5):​c.1733G>T​(p.Arg578Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27202898).

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>T	p.Arg578Leu	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>T	p.Arg578Leu	missense	Exon 16 of 29	ENSP00000512529.1
	TRPM5	ENST00000533060.5	TSL:1	c.1733G>T	p.Arg578Leu	missense	Exon 11 of 24	ENSP00000434121.1
	TRPM5	ENST00000528453.1	TSL:1	c.1733G>T	p.Arg578Leu	missense	Exon 11 of 24	ENSP00000436809.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1385774 Hom.: 0 Cov.: 67 AF XY: 0.00 AC XY: 0 AN XY: 682442

African (AFR) AF: 0.00 AC: 0 AN: 31288

American (AMR) AF: 0.00 AC: 0 AN: 35096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24930

East Asian (EAS) AF: 0.00 AC: 0 AN: 35468

South Asian (SAS) AF: 0.00 AC: 0 AN: 78734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4782

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1073528

Other (OTH) AF: 0.00 AC: 0 AN: 57374

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.00032	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.63	N
PhyloP100		3.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.26
Sift	Benign	0.12	T
Sift4G	Uncertain	0.054	T
Polyphen		0.072	B
Vest4		0.30
MutPred		0.32		Loss of disorder (P = 0.0371)
MVP		0.30
MPC		0.13
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.24
gMVP		0.26
Mutation Taster		=82/18	polymorphism

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;