Genetic Variant PMF1:c.162-6726C>T (chr1-156225594-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199654.2(PMF1):c.199C>T(p.Arg67Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,560,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PMF1
NM_001199654.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.46

Publications

0 publications found

Variant links:

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 links:

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-BGLAP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.08411449).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199654.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PMF1	NM_007221.4	MANE Select	c.162-6726C>T		intron	N/A	NP_009152.2	Q6P1K2-1
PMF1	NM_001199654.2		c.199C>T	p.Arg67Cys	missense	Exon 2 of 5	NP_001186583.1	Q6P1K2-2
PMF1	NM_001393910.1		c.199C>T	p.Arg67Cys	missense	Exon 2 of 5	NP_001380839.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PMF1	ENST00000368277.3	TSL:1 MANE Select	c.162-6726C>T	intron	N/A	ENSP00000357260.3	Q6P1K2-1
PMF1-BGLAP	ENST00000490491.5	TSL:2	c.162-6726C>T	intron	N/A	ENSP00000475561.1	U3KQ54
PMF1-BGLAP	ENST00000320139.5	TSL:1	c.162-6726C>T	intron	N/A	ENSP00000324909.5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000181

AC:

AN:

165620

AF XY:

0.0000223

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1408330

Hom.:

Cov.:

AF XY:

0.0000158

AC XY:

AN XY:

695802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32142

American (AMR)

AF:

0.00

AC:

AN:

37080

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25292

East Asian (EAS)

AF:

0.00

AC:

AN:

36822

South Asian (SAS)

AF:

0.000100

AC:

AN:

79894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

1084066

Other (OTH)

AF:

0.0000171

AC:

AN:

58428

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.0000267

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.15

(source)

DANN

Uncertain

0.98

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.53

M_CAP

Benign

0.0012

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.95

PhyloP100

-1.5

PROVEAN

Benign

-0.49

REVEL

Benign

0.022

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Vest4

0.11

MVP

0.048

ClinPred

0.054

GERP RS

-6.0

gMVP

0.45

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over