NM_001286581.2:c.470T>G

Variant names:

• chr11-591433-T-G
• rs1210504234
• NM_001286581.2:c.470T>G

Variant summary

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

The NM_001286581.2(PHRF1):​c.470T>G​(p.Ile157Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,438 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PHRF1 NM_001286581.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99
• 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.470T>G	p.Ile157Ser	missense	Exon 5 of 18	NP_001273510.1	Q9P1Y6-1
	PHRF1	NM_020901.4		c.470T>G	p.Ile157Ser	missense	Exon 5 of 18	NP_065952.2	Q9P1Y6-3
	PHRF1	NM_001286582.2		c.467T>G	p.Ile156Ser	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.470T>G	p.Ile157Ser	missense	Exon 5 of 18	ENSP00000264555.5	Q9P1Y6-1
	PHRF1	ENST00000416188.3	TSL:1	c.470T>G	p.Ile157Ser	missense	Exon 5 of 18	ENSP00000410626.2	Q9P1Y6-3
	PHRF1	ENST00000413872.6	TSL:1	c.467T>G	p.Ile156Ser	missense	Exon 5 of 18	ENSP00000388589.2	F8WEF5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243344 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000303

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457438 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724948

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.0000227 AC: 1 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39264

South Asian (SAS) AF: 0.00 AC: 0 AN: 85266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110262

Other (OTH) AF: 0.00 AC: 0 AN: 60214

GnomAD4 genome Cov.: 32

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	0.93
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.0071
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.0
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.73	P
Vest4		0.74
MutPred		0.45		Gain of catalytic residue at I157 (P = 0.0533)
MVP		0.55
MPC		0.47
ClinPred		0.98	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.58
gMVP		0.78
Mutation Taster		=76/24	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: rs1210504234; hg19: chr11-591433;