1-156236316-C-G

Position:

• chr1-156236316-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007221.4(PMF1):​c.397C>G​(p.Leu133Val) 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMF1 NM_007221.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.770

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]

PMF1 (HGNC:):

ACMG classification

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=0.106318295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMF1	NM_007221.4	c.397C>G	p.Leu133Val	missense_variant	4/5	ENST00000368277.3	NP_009152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMF1	ENST00000368277.3	c.397C>G	p.Leu133Val	missense_variant	4/5	1	NM_007221.4	ENSP00000357260.3
PMF1-BGLAP	ENST00000490491.5	c.397C>G	p.Leu133Val	missense_variant	4/7	2		ENSP00000475561.1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 26, 2024

The c.403C>G (p.L135V) alteration is located in exon 4 (coding exon 4) of the PMF1 gene. This alteration results from a C to G substitution at nucleotide position 403, causing the leucine (L) at amino acid position 135 to be replaced by a valine (V). 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	0.094
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.3
DANN	Benign	0.97
DEOGEN2	Benign	0.072	.;.;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	.;.;.;L
PROVEAN	Benign	-1.1	.;.;N;N
REVEL	Benign	0.021
Sift	Benign	0.14	.;.;T;T
Sift4G	Benign	0.40	T;T;T;T
Polyphen		0.17	.;.;.;B
Vest4		0.16
MutPred		0.50		Loss of helix (P = 0.0626);.;.;Loss of helix (P = 0.0626);
MVP		0.23
ClinPred		0.079	T
GERP RS		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-156206107;