chr11-69055249-C-T
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_139075.4(TPCN2):c.326C>T(p.Ala109Val) variant causes a missense change. The variant allele was found at a frequency of 0.000031 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
TPCN2
NM_139075.4 missense
NM_139075.4 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 4.78
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 -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.30374977).
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPCN2 | NM_139075.4 | c.326C>T | p.Ala109Val | missense_variant | 4/25 | ENST00000294309.8 | NP_620714.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TPCN2 | ENST00000294309.8 | c.326C>T | p.Ala109Val | missense_variant | 4/25 | 1 | NM_139075.4 | ENSP00000294309 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152262Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251390Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135888
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GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727234
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74394
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2021 | The c.326C>T (p.A109V) alteration is located in exon 4 (coding exon 4) of the TPCN2 gene. This alteration results from a C to T substitution at nucleotide position 326, causing the alanine (A) at amino acid position 109 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;T;D;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;D;.
REVEL
Benign
Sift
Uncertain
D;.;D;.
Sift4G
Uncertain
D;.;D;.
Polyphen
D;.;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
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gMVP
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