chr11-69062917-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_139075.4(TPCN2):ā€‹c.580T>Cā€‹(p.Phe194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000032 ( 0 hom. )

Consequence

TPCN2
NM_139075.4 missense

Scores

8
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TPCN2NM_139075.4 linkuse as main transcriptc.580T>C p.Phe194Leu missense_variant 6/25 ENST00000294309.8 NP_620714.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TPCN2ENST00000294309.8 linkuse as main transcriptc.580T>C p.Phe194Leu missense_variant 6/251 NM_139075.4 ENSP00000294309 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251362
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135846
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461734
Hom.:
0
Cov.:
31
AF XY:
0.0000481
AC XY:
35
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000510
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Skin/hair/eye pigmentation, variation in, 10 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingKasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.078
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D;T;D;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;.;D;D
M_CAP
Pathogenic
0.64
D
MetaRNN
Uncertain
0.60
D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.9
M;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-5.0
D;.;D;.
REVEL
Pathogenic
0.82
Sift
Uncertain
0.015
D;.;D;.
Sift4G
Benign
0.062
T;.;T;.
Polyphen
1.0
D;.;D;.
Vest4
0.71
MutPred
0.53
Loss of MoRF binding (P = 0.1175);Loss of MoRF binding (P = 0.1175);Loss of MoRF binding (P = 0.1175);Loss of MoRF binding (P = 0.1175);
MVP
0.86
MPC
0.81
ClinPred
0.94
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.87
gMVP
0.73

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: rs554622608; hg19: chr11-68830385; API