17-10825488-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001101387.2(PIRT):​c.158G>A​(p.Arg53His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PIRT
NM_001101387.2 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41
Variant links:
Genes affected
PIRT (HGNC:37239): (phosphoinositide interacting regulator of transient receptor potential channels) Predicted to enable phosphatidylinositol bisphosphate binding activity and transmembrane transporter binding activity. Predicted to be involved in phosphatidylinositol-mediated signaling and positive regulation of cation channel activity. Predicted to act upstream of or within behavioral response to pain and response to heat. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.023684412).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PIRTNM_001101387.2 linkc.158G>A p.Arg53His missense_variant Exon 2 of 2 ENST00000580256.3 NP_001094857.1 P0C851

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PIRTENST00000580256.3 linkc.158G>A p.Arg53His missense_variant Exon 2 of 2 2 NM_001101387.2 ENSP00000462046.1 P0C851
ENSG00000284876ENST00000643787.1 linkn.150+12457G>A intron_variant Intron 1 of 2
ENSG00000285220ENST00000647474.1 linkn.269-22404C>T intron_variant Intron 3 of 5

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152094
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000322
AC:
8
AN:
248636
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134898
show subpopulations
Gnomad AFR exome
AF:
0.000259
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000178
AC:
26
AN:
1461626
Hom.:
0
Cov.:
30
AF XY:
0.0000179
AC XY:
13
AN XY:
727074
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
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:
0.0000187
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152212
Hom.:
0
Cov.:
33
AF XY:
0.0000941
AC XY:
7
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.000241
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000413
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.158G>A (p.R53H) alteration is located in exon 2 (coding exon 1) of the PIRT gene. This alteration results from a G to A substitution at nucleotide position 158, causing the arginine (R) at amino acid position 53 to be replaced by a histidine (H). 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
Benign
0.085
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.058
T
Eigen
Benign
-0.50
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.024
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.64
N
PrimateAI
Benign
0.23
T
Sift4G
Benign
0.55
T
Polyphen
0.0060
B
Vest4
0.072
MVP
0.040
MPC
0.15
ClinPred
0.031
T
GERP RS
2.4
Varity_R
0.027
gMVP
0.20

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: rs372833831; hg19: chr17-10728805; API