chr11-591418-T-A

Variant names:

• chr11-591418-T-A
• rs767027832
• NM_001286581.2:c.455T>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001286581.2(PHRF1):​c.455T>A​(p.Phe152Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000373 in 1,610,310 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PHRF1 NM_001286581.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHRF1	NM_001286581.2	MANE Select	c.455T>A	p.Phe152Tyr	missense	Exon 5 of 18	NP_001273510.1	Q9P1Y6-1
	PHRF1	NM_020901.4		c.455T>A	p.Phe152Tyr	missense	Exon 5 of 18	NP_065952.2	Q9P1Y6-3
	PHRF1	NM_001286582.2		c.452T>A	p.Phe151Tyr	missense	Exon 5 of 18	NP_001273511.1	F8WEF5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHRF1	ENST00000264555.10	TSL:1 MANE Select	c.455T>A	p.Phe152Tyr	missense	Exon 5 of 18	ENSP00000264555.5	Q9P1Y6-1
	PHRF1	ENST00000416188.3	TSL:1	c.455T>A	p.Phe152Tyr	missense	Exon 5 of 18	ENSP00000410626.2	Q9P1Y6-3
	PHRF1	ENST00000413872.6	TSL:1	c.452T>A	p.Phe151Tyr	missense	Exon 5 of 18	ENSP00000388589.2	F8WEF5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152252 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 244080 AF XY: 0.00000754

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000570

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457940 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725228

African (AFR) AF: 0.00 AC: 0 AN: 33212

American (AMR) AF: 0.00 AC: 0 AN: 44118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.0000763 AC: 3 AN: 39344

South Asian (SAS) AF: 0.00 AC: 0 AN: 85352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110456

Other (OTH) AF: 0.00 AC: 0 AN: 60242

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152370 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74512

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.037
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.59		Loss of ubiquitination at K153 (P = 0.0699)
MVP		0.23
MPC		0.26
ClinPred		0.87	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.69
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs767027832; hg19: chr11-591418;