chr11-69055275-T-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_139075.4(TPCN2):āc.352T>Cā(p.Trp118Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 34)
Exomes š: 0.000014 ( 0 hom. )
Consequence
TPCN2
NM_139075.4 missense
NM_139075.4 missense
Scores
8
6
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.86
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.812
BS2
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPCN2 | NM_139075.4 | c.352T>C | p.Trp118Arg | missense_variant | 4/25 | ENST00000294309.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPCN2 | ENST00000294309.8 | c.352T>C | p.Trp118Arg | missense_variant | 4/25 | 1 | NM_139075.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251146Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135758
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1460890Hom.: 0 Cov.: 37 AF XY: 0.0000124 AC XY: 9AN XY: 726832
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152304Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74474
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Benign
DEOGEN2
Pathogenic
D;T;D;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.;T;T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;.
REVEL
Pathogenic
Sift
Benign
D;.;T;.
Sift4G
Uncertain
D;.;D;.
Polyphen
P;.;P;.
Vest4
MutPred
Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);Gain of disorder (P = 0.0012);
MVP
MPC
ClinPred
D
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at