GeneBe

rs11246212

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001286581.2(PHRF1):​c.4346T>A​(p.Val1449Glu) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PHRF1
NM_001286581.2 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.764

Publications

33 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043698937).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286581.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PHRF1
NM_001286581.2
MANE Select
c.4346T>Ap.Val1449Glu
missense
Exon 15 of 18NP_001273510.1
PHRF1
NM_020901.4
c.4343T>Ap.Val1448Glu
missense
Exon 15 of 18NP_065952.2
PHRF1
NM_001286582.2
c.4340T>Ap.Val1447Glu
missense
Exon 15 of 18NP_001273511.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
PHRF1
ENST00000264555.10
TSL:1 MANE Select
c.4346T>Ap.Val1449Glu
missense
Exon 15 of 18ENSP00000264555.5
PHRF1
ENST00000416188.3
TSL:1
c.4343T>Ap.Val1448Glu
missense
Exon 15 of 18ENSP00000410626.2
PHRF1
ENST00000413872.6
TSL:1
c.4340T>Ap.Val1447Glu
missense
Exon 15 of 18ENSP00000388589.2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1406662
Hom.:
0
Cov.:
70
AF XY:
0.00
AC XY:
0
AN XY:
694714
African (AFR)
AF:
0.00
AC:
0
AN:
31898
American (AMR)
AF:
0.00
AC:
0
AN:
37240
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25328
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36284
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79814
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48552
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1083524
Other (OTH)
AF:
0.00
AC:
0
AN:
58326
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
0.65
DANN
Benign
0.57
DEOGEN2
Benign
0.020
T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.087
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.0
N
PhyloP100
-0.76
PrimateAI
Benign
0.32
T
PROVEAN
Benign
0.040
N
REVEL
Benign
0.23
Sift
Benign
0.13
T
Sift4G
Uncertain
0.058
T
Polyphen
0.0
B
Vest4
0.30
MutPred
0.11
Gain of glycosylation at S1451 (P = 0.069)
MVP
0.082
MPC
0.15
ClinPred
0.075
T
GERP RS
-4.9
Varity_R
0.068
gMVP
0.12
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs11246212; hg19: chr11-610277; API