17-10825441-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001101387.2(PIRT):c.205G>A(p.Gly69Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000239 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
PIRT
NM_001101387.2 missense
NM_001101387.2 missense
Scores
2
8
6
Clinical Significance
Conservation
PhyloP100: 4.61
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIRT | NM_001101387.2 | c.205G>A | p.Gly69Ser | missense_variant | 2/2 | ENST00000580256.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIRT | ENST00000580256.3 | c.205G>A | p.Gly69Ser | missense_variant | 2/2 | 2 | NM_001101387.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000151 AC: 23AN: 152026Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000843 AC: 21AN: 248972Hom.: 0 AF XY: 0.0000963 AC XY: 13AN XY: 135060
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GnomAD4 exome AF: 0.000248 AC: 363AN: 1461700Hom.: 0 Cov.: 30 AF XY: 0.000234 AC XY: 170AN XY: 727134
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GnomAD4 genome AF: 0.000151 AC: 23AN: 152144Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN 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 | Oct 17, 2023 | The c.205G>A (p.G69S) 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 205, causing the glycine (G) at amino acid position 69 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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