11-581559-C-G

Variant names:

• chr11-581559-C-G
• NM_001286581.2:c.47C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286581.2(PHRF1):​c.47C>G​(p.Pro16Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHRF1 NM_001286581.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13192686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHRF1	NM_001286581.2	c.47C>G	p.Pro16Arg	missense_variant	Exon 2 of 18	ENST00000264555.10	NP_001273510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10	c.47C>G	p.Pro16Arg	missense_variant	Exon 2 of 18	1	NM_001286581.2	ENSP00000264555.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461186 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726878

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.;T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.0	M;.;.;M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.89	P;P;P;P
Vest4		0.30
MutPred		0.28		Gain of methylation at P16 (P = 0.0732);Gain of methylation at P16 (P = 0.0732);Gain of methylation at P16 (P = 0.0732);Gain of methylation at P16 (P = 0.0732);
MVP		0.12
MPC		0.45
ClinPred		0.49	T
GERP RS		2.6
Varity_R		0.048
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-581559;