Genetic Variant TRPM8:c.2761+259T>G (chr2-233983483-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024080.5(TRPM8):c.2761+259T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000328 in 305,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

TRPM8
NM_024080.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.72

Publications

0 publications found

Variant links:

Genes affected

TRPM8 (HGNC:17961): (transient receptor potential cation channel subfamily M member 8) Predicted to enable ligand-gated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within several processes, including cellular calcium ion homeostasis; response to cold; and thermoception. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TRPM8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM8	NM_024080.5 link	c.2761+259T>G		intron_variant	Intron 20 of 25	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9 link	c.2761+259T>G		intron_variant	Intron 20 of 25	1	NM_024080.5	ENSP00000323926.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000328

AC:

AN:

305112

Hom.:

AF XY:

0.00000618

AC XY:

AN XY:

161918

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8496

American (AMR)

AF:

0.00

AC:

AN:

13886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8382

East Asian (EAS)

AF:

0.00

AC:

AN:

16032

South Asian (SAS)

AF:

0.0000233

AC:

AN:

42918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1350

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

169804

Other (OTH)

AF:

0.00

AC:

AN:

16184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.067

(source)

DANN

Benign

0.44

PhyloP100

-3.7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over