Variant chr2-233955144-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000324695.9(TRPM8):c.1256G>A(p.Ser419Asn) variant causes a missense change. The variant allele was found at a frequency of 0.101 in 1,613,196 control chromosomes in the GnomAD database, including 22,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.22 ( 7390 hom., cov: 32)

Exomes 𝑓: 0.089 ( 14707 hom. )

Consequence

TRPM8
ENST00000324695.9 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.47

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7243624E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM8	NM_024080.5 linkuse as main transcript	c.1256G>A	p.Ser419Asn	missense_variant	11/26	ENST00000324695.9	NP_076985.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM8	ENST00000324695.9 linkuse as main transcript	c.1256G>A	p.Ser419Asn	missense_variant	11/26	1	NM_024080.5	ENSP00000323926	P1	Q7Z2W7-1
	ENST00000455991.1 linkuse as main transcript	n.292C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33281

AN:

152068

Hom.:

7355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.551

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.159

Gnomad ASJ

AF:

0.0695

Gnomad EAS

AF:

0.458

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.0296

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0519

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.148

AC:

37194

AN:

251112

Hom.:

5982

AF XY:

0.139

AC XY:

18863

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.559

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.0670

Gnomad EAS exome

AF:

0.463

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.0277

Gnomad NFE exome

AF:

0.0498

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.0891

AC:

130135

AN:

1461010

Hom.:

14707

Cov.:

AF XY:

0.0905

AC XY:

65774

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0676

Gnomad4 EAS exome

AF:

0.458

Gnomad4 SAS exome

AF:

0.212

Gnomad4 FIN exome

AF:

0.0292

Gnomad4 NFE exome

AF:

0.0509

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.219

AC:

33377

AN:

152186

Hom.:

7390

Cov.:

AF XY:

0.218

AC XY:

16243

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.551

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.0695

Gnomad4 EAS

AF:

0.459

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.0296

Gnomad4 NFE

AF:

0.0519

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.0893

Hom.:

3113

Bravo

AF:

0.240

TwinsUK

AF:

0.0564

AC:

209

ALSPAC

AF:

0.0566

AC:

218

ESP6500AA

AF:

0.530

AC:

2336

ESP6500EA

AF:

0.0580

AC:

499

ExAC

AF:

0.155

AC:

18770

Asia WGS

AF:

0.365

AC:

1270

AN:

3478

EpiCase

AF:

0.0508

EpiControl

AF:

0.0487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.074

T;T

MetaRNN

Benign

0.00017

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.63

PROVEAN

Benign

1.4

N;.

REVEL

Benign

0.076

Sift

Benign

0.88

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.076

MPC

0.14

ClinPred

0.0030

GERP RS

6.0

Varity_R

0.033

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over