22-21550753-C-T

Position:

chr22-21550753-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001128633.2(RIMBP3C):c.224G>A(p.Arg75His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.10 ( 0 hom., cov: 0)

Exomes 𝑓: 0.15 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3C
NM_001128633.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.426

Variant links:

Genes affected

RIMBP3C (HGNC:33892): (RIMS binding protein 3C) Predicted to enable benzodiazepine receptor binding activity. Predicted to be involved in fertilization and spermatid development. Predicted to be located in cytoplasm. Predicted to be active in nucleus. Predicted to colocalize with manchette. [provided by Alliance of Genome Resources, Apr 2022]

RIMBP3C links:

UBE2L3 (HGNC:12488): (ubiquitin conjugating enzyme E2 L3) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-kB precursor p105 in vitro. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

UBE2L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012536943).

BP6

Variant 22-21550753-C-T is Benign according to our data. Variant chr22-21550753-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2390705.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP3C	NM_001128633.2 linkuse as main transcript	c.224G>A	p.Arg75His	missense_variant	1/1	ENST00000433039.2	NP_001122105.1
UBE2L3	NM_001256355.1 linkuse as main transcript	c.201+1103C>T		intron_variant			NP_001243284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP3C	ENST00000433039.2 linkuse as main transcript	c.224G>A	p.Arg75His	missense_variant	1/1		NM_001128633.2	ENSP00000390630	P1
UBE2L3	ENST00000458578.6 linkuse as main transcript	c.201+1103C>T		intron_variant		2		ENSP00000400906		P68036-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

312

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0976

Gnomad AMR

AF:

0.0741

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.375

Gnomad NFE

AF:

0.0789

Gnomad OTH

AF:

0.167

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.154

AC:

17876

AN:

115850

Hom.:

Cov.:

AF XY:

0.155

AC XY:

8991

AN XY:

57936

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.244

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.101

AC:

AN:

318

Hom.:

Cov.:

AF XY:

0.108

AC XY:

AN XY:

176

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0741

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.143

Gnomad4 FIN

AF:

0.375

Gnomad4 NFE

AF:

0.0789

Gnomad4 OTH

AF:

0.167

Alfa

AF:

0.0733

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.064

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.0013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.41

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

2.0

REVEL

Benign

0.056

Sift

Benign

1.0

Sift4G

Benign

0.41

Vest4

0.12

MutPred

0.13

Gain of methylation at K79 (P = 0.0576);

MVP

0.067

ClinPred

0.15

GERP RS

3.7

Varity_R

0.037

gMVP

0.045

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