NM_007221.4:c.162-4731C>T

Variant names:

• chr1-156227589-C-T
• rs2984613
• NM_007221.4:c.162-4731C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007221.4(PMF1):​c.162-4731C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 149,198 control chromosomes in the GnomAD database, including 7,902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.32 (7902 hom., cov: 25)
• Consequence: PMF1 NM_007221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 35 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007221.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1	NM_007221.4	MANE Select	c.162-4731C>T		intron	N/A	NP_009152.2
	PMF1-BGLAP	NM_001199661.1		c.162-4731C>T		intron	N/A	NP_001186590.1
	PMF1-BGLAP	NM_001199662.1		c.162-4731C>T		intron	N/A	NP_001186591.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1	ENST00000368277.3	TSL:1 MANE Select	c.162-4731C>T		intron	N/A	ENSP00000357260.3
	PMF1-BGLAP	ENST00000490491.5	TSL:2	c.162-4731C>T		intron	N/A	ENSP00000475561.1
	PMF1-BGLAP	ENST00000320139.5	TSL:1	c.162-4731C>T		intron	N/A	ENSP00000324909.5

Frequencies

GnomAD3 genomes AF: 0.323 AC: 48093 AN: 149086 Hom.: 7899 Cov.: 25

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.332

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48114 AN: 149198 Hom.: 7902 Cov.: 25 AF XY: 0.321 AC XY: 23337 AN XY: 72646

African (AFR) AF: 0.271 AC: 11023 AN: 40638

American (AMR) AF: 0.322 AC: 4833 AN: 14996

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 963 AN: 3450

East Asian (EAS) AF: 0.329 AC: 1632 AN: 4954

South Asian (SAS) AF: 0.306 AC: 1426 AN: 4658

European-Finnish (FIN) AF: 0.346 AC: 3427 AN: 9900

Middle Eastern (MID) AF: 0.302 AC: 87 AN: 288

European-Non Finnish (NFE) AF: 0.353 AC: 23759 AN: 67342

Other (OTH) AF: 0.328 AC: 681 AN: 2074

Alfa AF: 0.330 Hom.: 1073

Bravo AF: 0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.84
DANN	Benign	0.91
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2984613; hg19: chr1-156197380;