19-49449489-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017916.3(PIH1D1):c.323C>A(p.Ala108Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PIH1D1
NM_017916.3 missense
NM_017916.3 missense
Scores
2
5
11
Clinical Significance
Conservation
PhyloP100: 6.87
Genes affected
PIH1D1 (HGNC:26075): (PIH1 domain containing 1) Enables several functions, including RNA polymerase I core promoter sequence-specific DNA binding activity; enzyme binding activity; and phosphoprotein binding activity. Involved in several processes, including box C/D snoRNP assembly; positive regulation of signal transduction; and regulation of cellular protein metabolic process. Located in cytoplasm and nucleolus. Part of R2TP complex and pre-snoRNP complex. [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 |
---|---|---|---|---|---|---|---|
PIH1D1 | NM_017916.3 | c.323C>A | p.Ala108Glu | missense_variant | 3/9 | ENST00000262265.10 | |
PIH1D1 | XM_047439025.1 | c.414C>A | p.Cys138Ter | stop_gained | 3/6 | ||
PIH1D1 | XM_047439024.1 | c.323C>A | p.Ala108Glu | missense_variant | 3/8 | ||
PIH1D1 | XM_024451570.2 | c.4C>A | p.Gln2Lys | missense_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIH1D1 | ENST00000262265.10 | c.323C>A | p.Ala108Glu | missense_variant | 3/9 | 1 | NM_017916.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Apr 11, 2023 | The c.323C>A (p.A108E) alteration is located in exon 3 (coding exon 3) of the PIH1D1 gene. This alteration results from a C to A substitution at nucleotide position 323, causing the alanine (A) at amino acid position 108 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.
REVEL
Benign
Sift
Benign
T;.;.;.;.
Sift4G
Benign
T;T;.;.;T
Polyphen
D;D;.;.;.
Vest4
MutPred
Gain of methylation at K113 (P = 0.0499);Gain of methylation at K113 (P = 0.0499);.;Gain of methylation at K113 (P = 0.0499);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.