Variant chr22-21547058-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001128633.2(RIMBP3C):c.3919C>A(p.Pro1307Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.58 ( 6166 hom. )

Failed GnomAD Quality Control

Consequence

RIMBP3C
NM_001128633.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.31

Variant links:

Genes affected

RIMBP3C (HGNC:33892): (RIMS binding protein 3C) 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]

RIMBP3C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060838252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP3C	NM_001128633.2 linkuse as main transcript	c.3919C>A	p.Pro1307Thr	missense_variant	1/1	ENST00000433039.2	NP_001122105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP3C	ENST00000433039.2 linkuse as main transcript	c.3919C>A	p.Pro1307Thr	missense_variant	1/1		NM_001128633.2	ENSP00000390630	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.578

AC:

26611

AN:

46062

Hom.:

6166

Cov.:

AF XY:

0.574

AC XY:

13614

AN XY:

23710

show subpopulations

Gnomad4 AFR exome

AF:

0.360

Gnomad4 AMR exome

AF:

0.671

Gnomad4 ASJ exome

AF:

0.624

Gnomad4 EAS exome

AF:

0.702

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.623

Gnomad4 NFE exome

AF:

0.592

Gnomad4 OTH exome

AF:

0.588

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:

0.515

Hom.:

590

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

Apr 27, 2022

The c.3919C>A (p.P1307T) alteration is located in exon 1 (coding exon 1) of the RIMBP3C gene. This alteration results from a C to A substitution at nucleotide position 3919, causing the proline (P) at amino acid position 1307 to be replaced by a threonine (T). 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

0.066

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.35

DANN

Benign

0.89

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.99

N;N

REVEL

Benign

0.013

Sift

Benign

0.044

D;D

Sift4G

Uncertain

0.044

D;D

Vest4

0.14

MVP

0.014

ClinPred

0.055

GERP RS

-5.4

Varity_R

0.034

gMVP

0.23

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