chr1-113704680-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001323043.2(PHTF1):c.1789C>T(p.Arg597Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000996 in 1,587,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000098 ( 0 hom. )
Consequence
PHTF1
NM_001323043.2 missense
NM_001323043.2 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 6.54
Genes affected
PHTF1 (HGNC:8939): (putative homeodomain transcription factor 1) Predicted to be located in cis-Golgi network and endoplasmic reticulum membrane. Predicted to be integral component of 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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.779
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHTF1 | NM_001323043.2 | c.1789C>T | p.Arg597Cys | missense_variant | 14/19 | ENST00000369604.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHTF1 | ENST00000369604.6 | c.1789C>T | p.Arg597Cys | missense_variant | 14/19 | 5 | NM_001323043.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000873 AC: 21AN: 240634Hom.: 0 AF XY: 0.0000692 AC XY: 9AN XY: 130104
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GnomAD4 exome AF: 0.0000976 AC: 140AN: 1434968Hom.: 0 Cov.: 26 AF XY: 0.0000923 AC XY: 66AN XY: 714838
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GnomAD4 genome AF: 0.000118 AC: 18AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74318
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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 | Jun 07, 2023 | The c.1789C>T (p.R597C) alteration is located in exon 13 (coding exon 13) of the PHTF1 gene. This alteration results from a C to T substitution at nucleotide position 1789, causing the arginine (R) at amino acid position 597 to be replaced by a cysteine (C). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;.;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D
Polyphen
D;.;.;D;D
Vest4
MVP
MPC
0.73
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -14
Find out detailed SpliceAI scores and Pangolin per-transcript scores at