1-156236426-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_007221.4(PMF1):c.507G>C(p.Gly169=) variant causes a synonymous 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMF1 NM_007221.4 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.443

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:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070839584).
• BP7: Synonymous conserved (PhyloP=-0.443 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMF1	NM_007221.4	c.507G>C	p.Gly169=	synonymous_variant	4/5	ENST00000368277.3
PMF1-BGLAP	NM_001199662.1	c.507G>C	p.Gly169=	synonymous_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMF1	ENST00000368277.3	c.507G>C	p.Gly169=	synonymous_variant	4/5	1	NM_007221.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.446G>C (p.G149A) alteration is located in exon 4 (coding exon 4) of the PMF1-BGLAP gene. This alteration results from a G to C substitution at nucleotide position 446, causing the glycine (G) at amino acid position 149 to be replaced by an alanine (A). 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
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	3.7
Dann	Uncertain	1.0
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.93	T
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.12
Sift	Benign	0.94	T;T
Sift4G	Benign	1.0	T;T
Vest4		0.31
MutPred		0.33		Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);
MVP		0.59
MPC		0.31
ClinPred		0.76	D
GERP RS		1.7
gMVP		0.018

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr1-156206217;