Genetic Variant RIMBP3B:p.Arg1019Cys (chr22-21386913-C-T) – 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.3055C>T(p.Arg1019Cys) 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: 0.000054 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3B
NM_001128635.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

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=0.14390776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMBP3B	NM_001128635.2 link	c.3055C>T	p.Arg1019Cys	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.3055C>T	p.Arg1019Cys	missense_variant	Exon 1 of 1	6	NM_001128635.2	ENSP00000479326.1		A6NNM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

1974

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000536

AC:

AN:

261298

Hom.:

Cov.:

AF XY:

0.0000498

AC XY:

AN XY:

140700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000995

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000724

Gnomad4 SAS exome

AF:

0.000160

Gnomad4 FIN exome

AF:

0.000159

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

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

AF:

0.00

AC:

AN:

1992

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

1004

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3055C>T (p.R1019C) alteration is located in exon 1 (coding exon 1) of the RIMBP3B gene. This alteration results from a C to T substitution at nucleotide position 3055, causing the arginine (R) at amino acid position 1019 to be replaced by a cysteine (C). 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

0.095

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.3

DANN

Benign

0.54

DEOGEN2

Benign

0.23

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.46

M_CAP

Benign

0.0096

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

PrimateAI

Benign

0.29

Sift4G

Uncertain

0.032

Vest4

0.098

MVP

0.15

ClinPred

0.29

GERP RS

0.78

Varity_R

0.088

gMVP

0.36

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over