rs1240608255

Variant names:

• chr1-156236426-G-C
• rs1240608255
• NM_007221.4:c.507G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-156236426-G-C
• chr1-156236426-G-A
• chr1-156236426-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199661.1(PMF1-BGLAP):​c.446G>C​(p.Gly149Ala) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G149G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMF1-BGLAP NM_001199661.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.443
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070839584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199661.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1	NM_007221.4	MANE Select	c.507G>C	p.Gly169Gly	synonymous	Exon 4 of 5	NP_009152.2	Q6P1K2-1
	PMF1-BGLAP	NM_001199661.1		c.446G>C	p.Gly149Ala	missense	Exon 4 of 7	NP_001186590.1	Q6P1K2-5
	PMF1	NM_001393910.1		c.452G>C	p.Gly151Ala	missense	Exon 4 of 5	NP_001380839.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1	ENST00000368277.3	TSL:1 MANE Select	c.507G>C	p.Gly169Gly	synonymous	Exon 4 of 5	ENSP00000357260.3	Q6P1K2-1
	PMF1-BGLAP	ENST00000490491.5	TSL:2	c.507G>C	p.Gly169Gly	synonymous	Exon 4 of 7	ENSP00000475561.1	U3KQ54
	PMF1-BGLAP	ENST00000320139.5	TSL:1	c.368+2698G>C		intron	N/A	ENSP00000324909.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
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
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.93	T
PhyloP100		-0.44
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.12
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Vest4		0.31
MutPred		0.33		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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs1240608255; hg19: chr1-156206217;