11-587352-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHRF1	NM_001286581.2	c.308A>T	p.Asp103Val	missense_variant	Exon 4 of 18	ENST00000264555.10	NP_001273510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHRF1	ENST00000264555.10	c.308A>T	p.Asp103Val	missense_variant	Exon 4 of 18	1	NM_001286581.2	ENSP00000264555.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Benign	0.047
Eigen_PC	Benign	-0.057
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D
Polyphen		0.96	D;D;D;D
Vest4		0.48
MutPred		0.31		Loss of disorder (P = 0.0268);.;.;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs201661078; hg19: chr11-587352;