chr11-587352-A-T

Variant names:

• chr11-587352-A-T
• rs201661078
• NM_001286581.2:c.308A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286581.2(PHRF1):​c.308A>T​(p.Asp103Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. D103G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHRF1 NM_001286581.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2734636).

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.308A>T	p.Asp103Val	missense	Exon 4 of 18	NP_001273510.1	Q9P1Y6-1
	PHRF1	NM_020901.4		c.308A>T	p.Asp103Val	missense	Exon 4 of 18	NP_065952.2	Q9P1Y6-3
	PHRF1	NM_001286582.2		c.305A>T	p.Asp102Val	missense	Exon 4 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.308A>T	p.Asp103Val	missense	Exon 4 of 18	ENSP00000264555.5	Q9P1Y6-1
	PHRF1	ENST00000416188.3	TSL:1	c.308A>T	p.Asp103Val	missense	Exon 4 of 18	ENSP00000410626.2	Q9P1Y6-3
	PHRF1	ENST00000413872.6	TSL:1	c.305A>T	p.Asp102Val	missense	Exon 4 of 18	ENSP00000388589.2	F8WEF5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.047
Eigen_PC	Benign	-0.057
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.2
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.96	D
Vest4		0.48
MutPred		0.31		Loss of disorder (P = 0.0268)
MVP		0.31
MPC		0.47
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.44
gMVP		0.39
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201661078; hg19: chr11-587352;