Variant chr22-21388657-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001128635.2(RIMBP3B):c.4799G>A(p.Gly1600Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 12)

Exomes 𝑓: 0.00066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3B
NM_001128635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP3B	NM_001128635.2 linkuse as main transcript	c.4799G>A	p.Gly1600Glu	missense_variant	1/1	ENST00000620804.2	NP_001122107.1	A6NNM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP3B	ENST00000620804.2 linkuse as main transcript	c.4799G>A	p.Gly1600Glu	missense_variant	1/1	6	NM_001128635.2	ENSP00000479326.1		A6NNM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

103194

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000220

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00110

Gnomad FIN

AF:

0.000301

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000474

Gnomad OTH

AF:

0.00172

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000665

AC:

731

AN:

1099268

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

371

AN XY:

553248

show subpopulations

Gnomad4 AFR exome

AF:

0.000113

Gnomad4 AMR exome

AF:

0.000290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000770

Gnomad4 FIN exome

AF:

0.000143

Gnomad4 NFE exome

AF:

0.000767

Gnomad4 OTH exome

AF:

0.000693

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000349

AC:

AN:

103194

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

48572

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000220

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00110

Gnomad4 FIN

AF:

0.000301

Gnomad4 NFE

AF:

0.000474

Gnomad4 OTH

AF:

0.00172

Alfa

AF:

0.000245

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

Jun 28, 2022

The c.4799G>A (p.G1600E) alteration is located in exon 1 (coding exon 1) of the RIMBP3B gene. This alteration results from a G to A substitution at nucleotide position 4799, causing the glycine (G) at amino acid position 1600 to be replaced by a glutamic acid (E). 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

0.43

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Benign

0.87

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.57

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

0.76

N;N

PrimateAI

Uncertain

0.68

Sift4G

Pathogenic

0.0

Vest4

0.73

MVP

0.35

ClinPred

0.97

GERP RS

3.0

Varity_R

0.21

gMVP

0.77

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