Variant chr22-29442093-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000354373.2(RFPL1):c.925G>A(p.Ala309Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,328 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RFPL1
ENST00000354373.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0750

Variant links:

Genes affected

RFPL1 (HGNC:9977): (ret finger protein like 1) Predicted to enable ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of G2/M transition of mitotic cell cycle; negative regulation of cell division; and positive regulation of proteolysis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RFPL1 links:

RFPL1S (HGNC:):

RFPL1S links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.065693766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
RFPL1	NM_021026.2 linkuse as main transcript	c.925G>A	p.Ala309Thr	missense_variant	2/2	NP_066306.2	O75677
RFPL1	NM_001393612.1 linkuse as main transcript	c.838G>A	p.Ala280Thr	missense_variant	10/10	NP_001380541.1
RFPL1S	NR_002727.2 linkuse as main transcript	n.37C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFPL1	ENST00000354373.2 linkuse as main transcript	c.925G>A	p.Ala309Thr	missense_variant	2/2	1		ENSP00000346342.2		O75677

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1434328

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709870

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.13e-7

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.925G>A (p.A309T) alteration is located in exon 2 (coding exon 2) of the RFPL1 gene. This alteration results from a G to A substitution at nucleotide position 925, causing the alanine (A) at amino acid position 309 to be replaced by a threonine (T). 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

0.071

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.2

DANN

Benign

0.34

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.00076

LIST_S2

Benign

0.42

M_CAP

Benign

0.011

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.67

REVEL

Benign

0.014

Sift

Benign

0.10

Sift4G

Benign

0.47

Polyphen

0.055

Vest4

0.013

MutPred

0.18

Gain of glycosylation at A309 (P = 0.0126);

MVP

0.34

MPC

0.18

ClinPred

0.024

GERP RS

-0.93

Varity_R

0.058

gMVP

0.097

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over