1-156239554-C-T

Variant names:

• chr1-156239554-C-T
• NM_007221.4:c.571C>T

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.571C>T​(p.His191Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PMF1 NM_007221.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.65
• 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=0.08519822).

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.571C>T	p.His191Tyr	missense	Exon 5 of 5	NP_009152.2	Q6P1K2-1
	PMF1	NM_001199654.2		c.577C>T	p.His193Tyr	missense	Exon 5 of 5	NP_001186583.1	Q6P1K2-2
	PMF1	NM_001393909.1		c.568C>T	p.His190Tyr	missense	Exon 5 of 5	NP_001380838.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMF1	ENST00000368277.3	TSL:1 MANE Select	c.571C>T	p.His191Tyr	missense	Exon 5 of 5	ENSP00000357260.3	Q6P1K2-1
	PMF1-BGLAP	ENST00000490491.5	TSL:2	c.565-2999C>T		intron	N/A	ENSP00000475561.1	U3KQ54
	PMF1-BGLAP	ENST00000320139.5	TSL:1	c.369-2999C>T		intron	N/A	ENSP00000324909.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.6
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.022
Sift	Benign	0.81	T
Sift4G	Benign	0.11	T
Polyphen		0.015	B
Vest4		0.32
MutPred		0.24		Gain of MoRF binding (P = 0.1388)
MVP		0.067
ClinPred		0.24	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.39
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

hg19: chr1-156209345;