1-156239554-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007221.4(PMF1):​c.571C>T​(p.His191Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PMF1
NM_007221.4 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65
Variant links:
Genes affected
PMF1 (HGNC:9112): (polyamine modulated factor 1) Enables leucine zipper domain binding activity and transcription coactivator activity. Involved in chromosome segregation. Located in Golgi apparatus; kinetochore; and nucleoplasm. Part of MIS12/MIND type complex. Implicated in bladder carcinoma and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]
PMF1-BGLAP (HGNC:42953): (PMF1-BGLAP readthrough) This locus represents naturally occurring read-through transcription between the neighboring PMF1 (polyamine-modulated factor 1) and BGLAP (bone gamma-carboxyglutamate Gla protein) genes on chromosome 1. Alternative splicing results in multiple transcript variants encoding isoforms that share sequence identity with the upstream gene product, but they contain distinct C-termini due to frameshifts versus the downstream gene coding sequence. [provided by RefSeq, Dec 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08519822).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PMF1NM_007221.4 linkc.571C>T p.His191Tyr missense_variant 5/5 ENST00000368277.3 NP_009152.2 Q6P1K2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PMF1ENST00000368277.3 linkc.571C>T p.His191Tyr missense_variant 5/51 NM_007221.4 ENSP00000357260.3 Q6P1K2-1
PMF1-BGLAPENST00000490491.5 linkc.565-2999C>T intron_variant 2 ENSP00000475561.1 U3KQ54

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
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 submitterclinical testingAmbry GeneticsMar 18, 2024The c.577C>T (p.H193Y) alteration is located in exon 5 (coding exon 5) of the PMF1 gene. This alteration results from a C to T substitution at nucleotide position 577, causing the histidine (H) at amino acid position 193 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.17
.;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.085
T;T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.022
Sift
Benign
0.81
T;T
Sift4G
Benign
0.11
T;T
Polyphen
0.015
.;B
Vest4
0.32
MutPred
0.24
.;Gain of MoRF binding (P = 0.1388);
MVP
0.067
ClinPred
0.24
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.13
gMVP
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156209345; API