dbSNP rs764819983: PHF1:p.Pro371Arg (chr6-33415017-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024165.3(PHF1):c.1112C>G(p.Pro371Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000382 in 1,572,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P371L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PHF1
NM_024165.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Variant links:

Genes affected

PHF1 (HGNC:8919): (PHD finger protein 1) This gene encodes a Polycomb group protein. The protein is a component of a histone H3 lysine-27 (H3K27)-specific methyltransferase complex, and functions in transcriptional repression of homeotic genes. The protein is also recruited to double-strand breaks, and reduced protein levels results in X-ray sensitivity and increased homologous recombination. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

PHF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027421296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF1	NM_024165.3 link	c.1112C>G	p.Pro371Arg	missense_variant	Exon 12 of 15	ENST00000374516.8	NP_077084.2	O43189-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHF1	ENST00000374516.8 link	c.1112C>G	p.Pro371Arg	missense_variant	Exon 12 of 15	1	NM_024165.3	ENSP00000363640.3		O43189-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000551

AC:

AN:

181640

Hom.:

AF XY:

0.0000102

AC XY:

AN XY:

98398

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000282

AC:

AN:

1420358

Hom.:

Cov.:

AF XY:

0.00000284

AC XY:

AN XY:

703412

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000266

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151920

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000844

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.061

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.80

M_CAP

Benign

0.0064

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.48

PROVEAN

Benign

0.32

REVEL

Benign

0.022

Sift

Benign

0.19

Sift4G

Benign

0.31

Polyphen

0.067

Vest4

0.20

MutPred

0.26

Loss of glycosylation at P371 (P = 0.0072);

MVP

0.27

MPC

1.1

ClinPred

0.027

GERP RS

0.99

Varity_R

0.037

gMVP

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over