1-156240066-C-T

Position:

• chr1-156240066-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001199661.1(PMF1-BGLAP):​c.504-2487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 157,184 control chromosomes in the GnomAD database, including 4,059 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 0.22 (3953 hom., cov: 32)
  • Exomes 𝑓: 0.19 (106 hom.)
• Consequence: PMF1-BGLAP NM_001199661.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

Genes affected

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: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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMF1	NM_007221.4	c.*465C>T		downstream_gene_variant		ENST00000368277.3	NP_009152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMF1-BGLAP	ENST00000490491.5	c.565-2487C>T		intron_variant		2		ENSP00000475561.1
PMF1	ENST00000368277.3	c.*465C>T		downstream_gene_variant		1	NM_007221.4	ENSP00000357260.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33585 AN: 152054 Hom.: 3936 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.187 AC: 935 AN: 5012 Hom.: 106 Cov.: 0 AF XY: 0.191 AC XY: 529 AN XY: 2770

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.212

Gnomad4 FIN exome AF: 0.109

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.221 AC: 33636 AN: 152172 Hom.: 3953 Cov.: 32 AF XY: 0.220 AC XY: 16394 AN XY: 74386

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.231

Alfa AF: 0.233 Hom.: 4222

Bravo AF: 0.237

Asia WGS AF: 0.290 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs1543294; hg19: chr1-156209857;