chr19-49447396-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_017916.3(PIH1D1):c.553C>T(p.Pro185Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,346 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PIH1D1
NM_017916.3 missense
NM_017916.3 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 5.08
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.553C>T | p.Pro185Ser | missense_variant | 6/9 | ENST00000262265.10 | |
PIH1D1 | XM_047439024.1 | c.553C>T | p.Pro185Ser | missense_variant | 6/8 | ||
PIH1D1 | XM_024451570.2 | c.172C>T | p.Pro58Ser | missense_variant | 3/6 | ||
PIH1D1 | XM_047439025.1 | downstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIH1D1 | ENST00000262265.10 | c.553C>T | p.Pro185Ser | missense_variant | 6/9 | 1 | NM_017916.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250828Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135644
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461346Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726998
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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1
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 02, 2023 | The c.553C>T (p.P185S) alteration is located in exon 6 (coding exon 6) of the PIH1D1 gene. This alteration results from a C to T substitution at nucleotide position 553, causing the proline (P) at amino acid position 185 to be replaced by a serine (S). 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
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.;.
Sift4G
Uncertain
D;D;.;.
Polyphen
D;D;.;.
Vest4
MutPred
Gain of phosphorylation at P185 (P = 0.0202);Gain of phosphorylation at P185 (P = 0.0202);.;.;
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