Variant 22-32358392-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000249007.4(RFPL3):c.321G>C(p.Glu107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000889 in 1,614,080 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

RFPL3
ENST00000249007.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.297

Variant links:

Genes affected

RFPL3 (HGNC:9980): (ret finger protein like 3) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be located in cytoplasm. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RFPL3 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=0.052455455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFPL3	NM_001098535.1 linkuse as main transcript	c.321G>C	p.Glu107Asp	missense_variant	1/2	ENST00000249007.4	NP_001092005.1	O75679-1
RFPL3	NM_006604.2 linkuse as main transcript	c.234G>C	p.Glu78Asp	missense_variant	2/3		NP_006595.1	O75679-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFPL3	ENST00000249007.4 linkuse as main transcript	c.321G>C	p.Glu107Asp	missense_variant	1/2	1	NM_001098535.1	ENSP00000249007.4		O75679-1
RFPL3	ENST00000397468.5 linkuse as main transcript	c.234G>C	p.Glu78Asp	missense_variant	2/3	1		ENSP00000380609.1		O75679-2

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000640

AC:

161

AN:

251448

Hom.:

AF XY:

0.000706

AC XY:

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000926

AC:

1354

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000945

AC XY:

687

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000532

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000941

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000872

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000692

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.00148

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

Aug 01, 2022

The c.321G>C (p.E107D) alteration is located in exon 1 (coding exon 1) of the RFPL3 gene. This alteration results from a G to C substitution at nucleotide position 321, causing the glutamic acid (E) at amino acid position 107 to be replaced by an aspartic acid (D). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0035

.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.049

Sift

Benign

0.040

D;T

Sift4G

Benign

0.21

T;T

Polyphen

1.0

.;D

Vest4

0.071

MutPred

0.35

.;Loss of helix (P = 0.0237);

MVP

0.65

MPC

0.70

ClinPred

0.97

GERP RS

0.66

Varity_R

0.32

gMVP

0.34

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