Variant 11-591418-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001286581.2(PHRF1):c.455T>A(p.Phe152Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,610,310 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PHRF1
NM_001286581.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

Variant links:

Genes affected

PHRF1 (HGNC:24351): (PHD and ring finger domains 1) Predicted to enable RNA polymerase binding activity. Predicted to be involved in mRNA processing and transcription by RNA polymerase II. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

PHRF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHRF1	NM_001286581.2 linkuse as main transcript	c.455T>A	p.Phe152Tyr	missense_variant	5/18	ENST00000264555.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHRF1	ENST00000264555.10 linkuse as main transcript	c.455T>A	p.Phe152Tyr	missense_variant	5/18	1	NM_001286581.2	P5	Q9P1Y6-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00000410

AC:

AN:

244080

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000570

Gnomad SAS 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:

0.00000206

AC:

AN:

1457940

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152370

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.455T>A (p.F152Y) alteration is located in exon 5 (coding exon 4) of the PHRF1 gene. This alteration results from a T to A substitution at nucleotide position 455, causing the phenylalanine (F) at amino acid position 152 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

T;T;T;T

M_CAP

Uncertain

0.22

MetaRNN

Uncertain

0.68

D;D;D;D

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.8

L;.;.;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

N;N;N;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.69

MutPred

0.59

Loss of ubiquitination at K153 (P = 0.0699);.;.;Loss of ubiquitination at K153 (P = 0.0699);

MVP

0.23

MPC

0.26

ClinPred

0.87

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over