Genetic Variant RIMBP3B:p.Ser1273Gly (chr22-21387675-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001128635.2(RIMBP3B):c.3817A>G(p.Ser1273Gly) 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 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.17 ( 1147 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3B
NM_001128635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.183

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 Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.073001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMBP3B	NM_001128635.2 link	c.3817A>G	p.Ser1273Gly	missense_variant	Exon 1 of 1	ENST00000620804.2	NP_001122107.1	A6NNM3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMBP3B	ENST00000620804.2 link	c.3817A>G	p.Ser1273Gly	missense_variant	Exon 1 of 1	6	NM_001128635.2	ENSP00000479326.1		A6NNM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.166

AC:

12758

AN:

76644

Hom.:

1147

Cov.:

AF XY:

0.166

AC XY:

7376

AN XY:

44442

show subpopulations

Gnomad4 AFR exome

AF:

0.248

Gnomad4 AMR exome

AF:

0.390

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.326

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.0917

Gnomad4 NFE exome

AF:

0.0889

Gnomad4 OTH exome

AF:

0.159

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0531

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3817A>G (p.S1273G) alteration is located in exon 1 (coding exon 1) of the RIMBP3B gene. This alteration results from a A to G substitution at nucleotide position 3817, causing the serine (S) at amino acid position 1273 to be replaced by a glycine (G). 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

0.081

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.6

DANN

Benign

0.77

DEOGEN2

Benign

0.025

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.30

M_CAP

Benign

0.0073

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.31

Sift4G

Benign

0.090

Vest4

0.085

MVP

0.030

ClinPred

0.070

GERP RS

-1.7

Varity_R

0.039

gMVP

0.19

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