NM_007221.4:c.162-6680C>G

Variant names:

• chr1-156225640-C-G
• rs1055553309
• NM_007221.4:c.162-6680C>G

Variant summary

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

The NM_007221.4(PMF1):​c.162-6680C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,409,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PMF1 NM_007221.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• 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=0.110031486).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1	NM_007221.4	MANE Select	c.162-6680C>G		intron	N/A	NP_009152.2	Q6P1K2-1
	PMF1	NM_001199654.2		c.245C>G	p.Ala82Gly	missense	Exon 2 of 5	NP_001186583.1	Q6P1K2-2
	PMF1	NM_001393910.1		c.245C>G	p.Ala82Gly	missense	Exon 2 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.162-6680C>G		intron	N/A	ENSP00000357260.3	Q6P1K2-1
	PMF1-BGLAP	ENST00000490491.5	TSL:2	c.162-6680C>G		intron	N/A	ENSP00000475561.1	U3KQ54
	PMF1-BGLAP	ENST00000320139.5	TSL:1	c.162-6680C>G		intron	N/A	ENSP00000324909.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1409396 Hom.: 0 Cov.: 30 AF XY: 0.00000144 AC XY: 1 AN XY: 696384

African (AFR) AF: 0.00 AC: 0 AN: 32198

American (AMR) AF: 0.00 AC: 0 AN: 37184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.00 AC: 0 AN: 36940

South Asian (SAS) AF: 0.00 AC: 0 AN: 80034

European-Finnish (FIN) AF: 0.0000408 AC: 2 AN: 48988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084580

Other (OTH) AF: 0.00 AC: 0 AN: 58444

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.8
DANN	Benign	0.75
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.090
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.014
Sift	Benign	0.36	T
Sift4G	Benign	0.073	T
Vest4		0.42
MutPred		0.48		Loss of helix (P = 0.0072)
MVP		0.040
ClinPred		0.039	T
GERP RS		0.029
gMVP		0.56
Mutation Taster		=82/18	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: rs1055553309; hg19: chr1-156195431;