Variant chr11-69054796-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_139075.4(TPCN2):c.250C>T(p.Arg84Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000794 in 1,613,920 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00075 ( 11 hom. )

Consequence

TPCN2
NM_139075.4 missense, splice_region

Scores

Splicing: ADA: 0.001273

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.909

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004129082).

BP6

Variant 11-69054796-C-T is Benign according to our data. Variant chr11-69054796-C-T is described in ClinVar as [Benign]. Clinvar id is 708141.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0012 (183/152334) while in subpopulation EAS AF= 0.0295 (153/5188). AF 95% confidence interval is 0.0257. There are 3 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 183 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPCN2	NM_139075.4 linkuse as main transcript	c.250C>T	p.Arg84Trp	missense_variant, splice_region_variant	3/25	ENST00000294309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPCN2	ENST00000294309.8 linkuse as main transcript	c.250C>T	p.Arg84Trp	missense_variant, splice_region_variant	3/25	1	NM_139075.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0294

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00217

AC:

544

AN:

250864

Hom.:

AF XY:

0.00200

AC XY:

271

AN XY:

135604

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000580

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0281

Gnomad SAS exome

AF:

0.000426

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000752

AC:

1099

AN:

1461586

Hom.:

Cov.:

AF XY:

0.000703

AC XY:

511

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0234

Gnomad4 SAS exome

AF:

0.000569

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000504

Gnomad4 OTH exome

AF:

0.000878

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152334

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0295

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.00145

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00213

AC:

258

Asia WGS

AF:

0.00808

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.097

T;T;T;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.31

LIST_S2

Uncertain

0.90

D;.;D;D

MetaRNN

Benign

0.0041

T;T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Benign

-0.18

N;.;.;.

MutationTaster

Benign

0.70

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.96

N;.;N;.

REVEL

Uncertain

0.33

Sift

Benign

0.20

T;.;T;.

Sift4G

Benign

0.18

T;.;T;.

Polyphen

0.0020

B;.;B;.

Vest4

0.34

MVP

0.65

MPC

0.20

ClinPred

0.036

GERP RS

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.043

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

dbscSNV1_RF

Benign

0.052

SpliceAI score (max)

0.010

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