chr19-49446654-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017916.3(PIH1D1):c.728G>A(p.Arg243His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000879 in 1,593,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000083 ( 0 hom. )
Consequence
PIH1D1
NM_017916.3 missense
NM_017916.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: -0.0160
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.728G>A | p.Arg243His | missense_variant | 8/9 | ENST00000262265.10 | |
PIH1D1 | XM_024451570.2 | c.347G>A | p.Arg116His | missense_variant | 5/6 | ||
PIH1D1 | XM_047439024.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIH1D1 | ENST00000262265.10 | c.728G>A | p.Arg243His | missense_variant | 8/9 | 1 | NM_017916.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000857 AC: 2AN: 233386Hom.: 0 AF XY: 0.00000795 AC XY: 1AN XY: 125764
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GnomAD4 exome AF: 0.00000833 AC: 12AN: 1441158Hom.: 0 Cov.: 33 AF XY: 0.0000112 AC XY: 8AN XY: 715110
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74316
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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 | May 05, 2023 | The c.728G>A (p.R243H) alteration is located in exon 8 (coding exon 8) of the PIH1D1 gene. This alteration results from a G to A substitution at nucleotide position 728, causing the arginine (R) at amino acid position 243 to be replaced by a histidine (H). 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
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Benign
T;.;.
Sift4G
Uncertain
D;D;.
Polyphen
B;B;.
Vest4
MutPred
Gain of disorder (P = 0.2333);Gain of disorder (P = 0.2333);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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