22-32191021-G-T

Position:

• chr22-32191021-G-T

Variant summary

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

The NM_001394555.1(RFPL2):​c.888C>A​(p.Phe296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: RFPL2 NM_001394555.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.25

Genes affected

RFPL2 (HGNC:9979): (ret finger protein like 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RFPL2 (HGNC:):

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=0.12086049).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFPL2	NM_001394555.1	c.888C>A	p.Phe296Leu	missense_variant	5/5	ENST00000652607.2	NP_001381484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFPL2	ENST00000652607.2	c.888C>A	p.Phe296Leu	missense_variant	5/5		NM_001394555.1	ENSP00000498332.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 59

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.888C>A (p.F296L) alteration is located in exon 5 (coding exon 4) of the RFPL2 gene. This alteration results from a C to A substitution at nucleotide position 888, causing the phenylalanine (F) at amino acid position 296 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.8
DANN	Benign	0.52
DEOGEN2	Benign	0.0016	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.20	T;T;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.14	.;N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.39	N;.;N
REVEL	Benign	0.013
Sift	Benign	0.37	T;.;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.036	B;B;B
Vest4		0.051
MutPred		0.33		.;Gain of catalytic residue at F296 (P = 0.0536);Gain of catalytic residue at F296 (P = 0.0536);
MVP		0.53
MPC		0.69
ClinPred		0.14	T
GERP RS		0.35
Varity_R		0.085
gMVP		0.13

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: chr22-32587008;