Variant 22-18607438-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_015672.2(RIMBP3):c.3997G>A(p.Glu1333Lys) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 1 hom., cov: 18)

Exomes 𝑓: 0.00019 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3
NM_015672.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.129

Variant links:

Genes affected

RIMBP3 (HGNC:29344): (RIMS binding protein 3) 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]

RIMBP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058190256).

BP6

Variant 22-18607438-C-T is Benign according to our data. Variant chr22-18607438-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2343600.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP3	NM_015672.2 linkuse as main transcript	c.3997G>A	p.Glu1333Lys	missense_variant	1/1	ENST00000619918.1	NP_056487.1	Q9UFD9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP3	ENST00000619918.1 linkuse as main transcript	c.3997G>A	p.Glu1333Lys	missense_variant	1/1	6	NM_015672.2	ENSP00000483386.1		Q9UFD9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

113152

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000802

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000311

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000720

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000769

AC:

AN:

130016

Hom.:

AF XY:

0.0000714

AC XY:

AN XY:

69994

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.0000753

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000262

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000191

AC:

257

AN:

1348434

Hom.:

Cov.:

AF XY:

0.000214

AC XY:

144

AN XY:

671530

show subpopulations

Gnomad4 AFR exome

AF:

0.000204

Gnomad4 AMR exome

AF:

0.000451

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000729

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.000323

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000133

AC:

AN:

113152

Hom.:

Cov.:

AF XY:

0.0000369

AC XY:

AN XY:

54244

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.000802

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000311

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000720

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000243

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

DANN

Benign

0.83

DEOGEN2

Benign

0.0086

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.55

M_CAP

Benign

0.0035

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

Sift4G

Benign

0.30

Vest4

0.18

MVP

0.030

ClinPred

0.0081

GERP RS

-0.26

Varity_R

0.029

gMVP

0.26

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