Variant 22-21387646-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001128635.2(RIMBP3B):c.3788A>C(p.Glu1263Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.25 ( 0 hom., cov: 0)

Exomes 𝑓: 0.17 ( 1248 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3B
NM_001128635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

Variant links:

Genes affected

RIMBP3B (HGNC:33891): (RIMS binding protein 3B) 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]

RIMBP3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10921261).

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP3B	NM_001128635.2 linkuse as main transcript	c.3788A>C	p.Glu1263Ala	missense_variant	1/1	ENST00000620804.2	NP_001122107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP3B	ENST00000620804.2 linkuse as main transcript	c.3788A>C	p.Glu1263Ala	missense_variant	1/1		NM_001128635.2	ENSP00000479326	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

Gnomad EAS

AF:

0.00

GnomAD4 exome

AF:

0.165

AC:

14386

AN:

87098

Hom.:

1248

Cov.:

AF XY:

0.164

AC XY:

8209

AN XY:

50050

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.346

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.0983

Gnomad4 NFE exome

AF:

0.0930

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.500

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0390

Hom.:

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

Mar 31, 2022

The c.3788A>C (p.E1263A) alteration is located in exon 1 (coding exon 1) of the RIMBP3B gene. This alteration results from a A to C substitution at nucleotide position 3788, causing the glutamic acid (E) at amino acid position 1263 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.030

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.53

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.42

Sift4G

Benign

0.34

Vest4

0.16

MVP

0.072

ClinPred

0.57

GERP RS

3.2

Varity_R

0.066

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