Variant rs3829241 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139075.4(TPCN2):c.2201G>A(p.Gly734Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,611,286 control chromosomes in the GnomAD database, including 106,973 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.28 ( 7160 hom., cov: 32)

Exomes 𝑓: 0.36 ( 99813 hom. )

Consequence

TPCN2
NM_139075.4 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

TPCN2 (HGNC:20820): (two pore segment channel 2) This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

TPCN2 links:

ENSG00000287725 (HGNC:):

ENSG00000287725 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=0.0012671053).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPCN2	NM_139075.4 linkuse as main transcript	c.2201G>A	p.Gly734Glu	missense_variant	25/25	ENST00000294309.8	NP_620714.2	Q8NHX9Q59G56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPCN2	ENST00000294309.8 linkuse as main transcript	c.2201G>A	p.Gly734Glu	missense_variant	25/25	1	NM_139075.4	ENSP00000294309.3		Q8NHX9
ENSG00000287725	ENST00000637084.1 linkuse as main transcript	n.1058G>A		non_coding_transcript_exon_variant	13/15	1		ENSP00000490615.1		A0A1B0GVQ7

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42048

AN:

151896

Hom.:

7162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0959

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.184

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.293

GnomAD3 exomes

AF:

0.289

AC:

71251

AN:

246832

Hom.:

11891

AF XY:

0.289

AC XY:

38682

AN XY:

133836

show subpopulations

Gnomad AFR exome

AF:

0.0897

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.257

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.368

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.358

AC:

522122

AN:

1459272

Hom.:

99813

Cov.:

AF XY:

0.352

AC XY:

255523

AN XY:

725836

show subpopulations

Gnomad4 AFR exome

AF:

0.0805

Gnomad4 AMR exome

AF:

0.202

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.229

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.373

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.276

AC:

42026

AN:

152014

Hom.:

7160

Cov.:

AF XY:

0.271

AC XY:

20152

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0957

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.274

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.353

Hom.:

20413

Bravo

AF:

0.265

TwinsUK

AF:

0.399

AC:

1478

ALSPAC

AF:

0.423

AC:

1631

ESP6500AA

AF:

0.106

AC:

466

ESP6500EA

AF:

0.383

AC:

3292

ExAC

AF:

0.288

AC:

34934

Asia WGS

AF:

0.160

AC:

558

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Skin/hair/eye pigmentation, variation in, 10

Other:1

association, no assertion criteria provided

literature only

OMIM

May 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.31

CADD

Benign

8.4

DANN

Benign

0.70

DEOGEN2

Benign

0.097

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.22

PROVEAN

Benign

0.78

N;N

REVEL

Benign

0.25

Sift

Benign

1.0

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.0010

B;B

Vest4

0.057

MPC

0.25

ClinPred

0.00058

GERP RS

-3.6

Varity_R

0.030

gMVP

0.32

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over