Genetic Variant RIMBP3B:p.Arg1019Cys (chr22-21386913-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 14/19 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14390776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128635.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP3B	NM_001128635.2	MANE Select	c.3055C>T	p.Arg1019Cys	missense	Exon 1 of 1	NP_001122107.1	A6NNM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIMBP3B	ENST00000620804.2	TSL:6 MANE Select	c.3055C>T	p.Arg1019Cys	missense	Exon 1 of 1	ENSP00000479326.1	A6NNM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

1974

Hom.:

Cov.:

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

2984

American (AMR)

AF:

0.0000995

AC:

AN:

20110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6780

East Asian (EAS)

AF:

0.0000724

AC:

AN:

27616

South Asian (SAS)

AF:

0.000160

AC:

AN:

50076

European-Finnish (FIN)

AF:

0.000159

AC:

AN:

12578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1236

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

126218

Other (OTH)

AF:

0.00

AC:

AN:

13700

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000438497), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

400

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

566

South Asian (SAS)

AF:

0.00

AC:

AN:

304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

304

Other (OTH)

AF:

0.00

AC:

AN:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.3

(source)

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

PhyloP100

1.9

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

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over