11-69087765-G-A

Variant summary

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

The NM_139075.4(TPCN2):​c.2181-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 780,160 control chromosomes in the GnomAD database, including 79,865 homozygotes. 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: 𝑓 0.45 ( 15684 hom., cov: 32)
Exomes 𝑓: 0.44 ( 64181 hom. )

Consequence

TPCN2
NM_139075.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610
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]

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 (BayesDel_noAF=-0.8).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TPCN2NM_139075.4 linkuse as main transcriptc.2181-110G>A intron_variant ENST00000294309.8 NP_620714.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TPCN2ENST00000294309.8 linkuse as main transcriptc.2181-110G>A intron_variant 1 NM_139075.4 ENSP00000294309 P1

Frequencies

GnomAD3 genomes
AF:
0.448
AC:
68101
AN:
151938
Hom.:
15684
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.408
Gnomad AMI
AF:
0.677
Gnomad AMR
AF:
0.393
Gnomad ASJ
AF:
0.493
Gnomad EAS
AF:
0.298
Gnomad SAS
AF:
0.225
Gnomad FIN
AF:
0.480
Gnomad MID
AF:
0.405
Gnomad NFE
AF:
0.502
Gnomad OTH
AF:
0.464
GnomAD4 exome
AF:
0.443
AC:
278517
AN:
628104
Hom.:
64181
AF XY:
0.436
AC XY:
142020
AN XY:
325592
show subpopulations
Gnomad4 AFR exome
AF:
0.400
Gnomad4 AMR exome
AF:
0.329
Gnomad4 ASJ exome
AF:
0.484
Gnomad4 EAS exome
AF:
0.307
Gnomad4 SAS exome
AF:
0.235
Gnomad4 FIN exome
AF:
0.477
Gnomad4 NFE exome
AF:
0.484
Gnomad4 OTH exome
AF:
0.449
GnomAD4 genome
AF:
0.448
AC:
68113
AN:
152056
Hom.:
15684
Cov.:
32
AF XY:
0.440
AC XY:
32686
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.407
Gnomad4 AMR
AF:
0.392
Gnomad4 ASJ
AF:
0.493
Gnomad4 EAS
AF:
0.298
Gnomad4 SAS
AF:
0.225
Gnomad4 FIN
AF:
0.480
Gnomad4 NFE
AF:
0.502
Gnomad4 OTH
AF:
0.459
Alfa
AF:
0.313
Hom.:
781
Bravo
AF:
0.446
Asia WGS
AF:
0.288
AC:
1004
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
5.6
DANN
Benign
0.77

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.

Other links and lift over

dbSNP: rs1551305; hg19: chr11-68855233; API