22-32190861-G-A

Position:

• chr22-32190861-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394555.1(RFPL2):​c.1048C>T​(p.Pro350Ser) 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. 16/21 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: 0.307

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059026778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFPL2	NM_001394555.1	c.1048C>T	p.Pro350Ser	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.1048C>T	p.Pro350Ser	missense_variant	5/5		NM_001394555.1	ENSP00000498332	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Feb 14, 2024

The c.1048C>T (p.P350S) alteration is located in exon 5 (coding exon 4) of the RFPL2 gene. This alteration results from a C to T substitution at nucleotide position 1048, causing the proline (P) at amino acid position 350 to be replaced by a serine (S). 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	Benign	0.10
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.3
DANN	Benign	0.29
DEOGEN2	Benign	0.00093	.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0096	N
LIST_S2	Benign	0.27	T;T;.
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.10	.;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N;.;N
REVEL	Benign	0.027
Sift	Benign	0.80	T;.;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.022	B;B;B
Vest4		0.037
MutPred		0.28		.;Loss of catalytic residue at P349 (P = 0.0194);Loss of catalytic residue at P349 (P = 0.0194);
MVP		0.28
MPC		0.49
ClinPred		0.052	T
GERP RS		-0.78
Varity_R		0.028
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs1169144713; hg19: chr22-32586848;