chr11-69057627-G-A

Variant summary

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

The NM_139075.4(TPCN2):​c.479G>A​(p.Gly160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TPCN2
NM_139075.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.536
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 GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TPCN2NM_139075.4 linkuse as main transcriptc.479G>A p.Gly160Asp missense_variant 5/25 ENST00000294309.8 NP_620714.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TPCN2ENST00000294309.8 linkuse as main transcriptc.479G>A p.Gly160Asp missense_variant 5/251 NM_139075.4 ENSP00000294309 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461878
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsMay 27, 2022The c.479G>A (p.G160D) alteration is located in exon 5 (coding exon 5) of the TPCN2 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the glycine (G) at amino acid position 160 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Uncertain
0.096
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D;T;D;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.70
T;.;T;T
M_CAP
Pathogenic
0.30
D
MetaRNN
Uncertain
0.51
D;D;D;D
MetaSVM
Uncertain
0.53
D
MutationAssessor
Benign
1.0
L;.;.;.
MutationTaster
Benign
0.99
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.2
D;.;D;.
REVEL
Uncertain
0.47
Sift
Benign
0.035
D;.;D;.
Sift4G
Benign
0.073
T;.;T;.
Polyphen
0.73
P;.;P;.
Vest4
0.35
MutPred
0.72
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.72
MPC
0.25
ClinPred
0.71
D
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.38
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-68825095; API