11-581597-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000264555.10(PHRF1):​c.85G>A​(p.Gly29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,460,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

PHRF1
ENST00000264555.10 missense

Scores

1
15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.490
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058318734).
BP6
Variant 11-581597-G-A is Benign according to our data. Variant chr11-581597-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2611032.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PHRF1NM_001286581.2 linkuse as main transcriptc.85G>A p.Gly29Ser missense_variant 2/18 ENST00000264555.10 NP_001273510.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PHRF1ENST00000264555.10 linkuse as main transcriptc.85G>A p.Gly29Ser missense_variant 2/181 NM_001286581.2 ENSP00000264555 P5Q9P1Y6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000204
AC:
5
AN:
244934
Hom.:
0
AF XY:
0.0000374
AC XY:
5
AN XY:
133748
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 SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1460134
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
726298
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000248
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 12, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.066
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
16
DANN
Benign
0.72
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0042
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.058
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.24
Sift
Uncertain
0.011
D
Sift4G
Benign
0.64
T
Polyphen
0.0
B
Vest4
0.091
MutPred
0.15
Gain of ubiquitination at E29 (P = 0.0016);
MVP
0.11
ClinPred
0.026
T
GERP RS
-0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs749479153; hg19: chr11-581597; API