rs2758605

chr1-156230654-G-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PMF1	NM_007221.4	c.162-1666G>C		intron_variant		ENST00000368277.3
PMF1-BGLAP	NM_001199662.1	c.162-1666G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMF1	ENST00000368277.3	c.162-1666G>C		intron_variant		1	NM_007221.4	P1

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

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.357

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

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: rs2758605; hg19: chr1-156200445;