NM_001286581.2:c.35G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001286581.2(PHRF1):​c.35G>A​(p.Arg12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R12P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

PHRF1
NM_001286581.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0160
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.040232062).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHRF1NM_001286581.2 linkc.35G>A p.Arg12Gln missense_variant Exon 2 of 18 ENST00000264555.10 NP_001273510.1 Q9P1Y6-1A0A024RCA1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHRF1ENST00000264555.10 linkc.35G>A p.Arg12Gln missense_variant Exon 2 of 18 1 NM_001286581.2 ENSP00000264555.5 Q9P1Y6-1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152178
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000403
AC:
10
AN:
248230
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135068
show subpopulations
Gnomad AFR exome
AF:
0.0000649
Gnomad AMR exome
AF:
0.0000290
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:
0.0000713
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000931
AC:
136
AN:
1461246
Hom.:
0
Cov.:
31
AF XY:
0.0000894
AC XY:
65
AN XY:
726908
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000118
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152178
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
8.0
DANN
Benign
0.94
DEOGEN2
Benign
0.020
T;.;T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.75
T;T;T;T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.040
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.27
N;.;.;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.18
Sift
Benign
0.17
T;T;T;T
Sift4G
Benign
0.13
T;T;T;T
Polyphen
0.0070
B;B;B;B
Vest4
0.10
MutPred
0.12
Gain of glycosylation at S13 (P = 0.1004);Gain of glycosylation at S13 (P = 0.1004);Gain of glycosylation at S13 (P = 0.1004);Gain of glycosylation at S13 (P = 0.1004);
MVP
0.18
MPC
0.10
ClinPred
0.016
T
GERP RS
-1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.022
gMVP
0.081

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.

Other links and lift over

dbSNP: rs371292036; hg19: chr11-581547; COSMIC: COSV52752096; API