rs2758605

Variant names:

• chr1-156230654-G-C
• rs2758605
• NM_007221.4:c.162-1666G>C

Variant summary

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

The NM_007221.4(PMF1):​c.162-1666G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,992 control chromosomes in the GnomAD database, including 10,307 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 0.37 (10307 hom., cov: 31)
• Consequence: PMF1 NM_007221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMF1	NM_007221.4	c.162-1666G>C		intron_variant	Intron 1 of 4	ENST00000368277.3	NP_009152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMF1	ENST00000368277.3	c.162-1666G>C		intron_variant	Intron 1 of 4	1	NM_007221.4	ENSP00000357260.3
PMF1-BGLAP	ENST00000490491.5	c.162-1666G>C		intron_variant	Intron 1 of 6	2		ENSP00000475561.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55594 AN: 151874 Hom.: 10291 Cov.: 31

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.366 AC: 55646 AN: 151992 Hom.: 10307 Cov.: 31 AF XY: 0.364 AC XY: 27069 AN XY: 74306

African (AFR) AF: 0.414 AC: 17174 AN: 41438

American (AMR) AF: 0.338 AC: 5161 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1757 AN: 5170

South Asian (SAS) AF: 0.318 AC: 1534 AN: 4818

European-Finnish (FIN) AF: 0.356 AC: 3754 AN: 10552

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24160 AN: 67958

Other (OTH) AF: 0.357 AC: 754 AN: 2110

Alfa AF: 0.366 Hom.: 1250

Bravo AF: 0.365

Asia WGS AF: 0.330 AC: 1148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.82
DANN	Benign	0.64
PhyloP100		-0.34
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: rs2758605; hg19: chr1-156200445;