22-21546179-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001128633.2(RIMBP3C):​c.4798G>C​(p.Gly1600Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 5)

Consequence

RIMBP3C
NM_001128633.2 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.887

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RIMBP3CNM_001128633.2 linkuse as main transcriptc.4798G>C p.Gly1600Arg missense_variant 1/1 ENST00000433039.2 NP_001122105.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RIMBP3CENST00000433039.2 linkuse as main transcriptc.4798G>C p.Gly1600Arg missense_variant 1/1 NM_001128633.2 ENSP00000390630 P1

Frequencies

GnomAD3 genomes
Cov.:
5
GnomAD4 exome
Cov.:
4
GnomAD4 genome
Cov.:
5

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 submitterclinical testingAmbry GeneticsApr 07, 2022The c.4798G>C (p.G1600R) alteration is located in exon 1 (coding exon 1) of the RIMBP3C gene. This alteration results from a G to C substitution at nucleotide position 4798, causing the glycine (G) at amino acid position 1600 to be replaced by an arginine (R). 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
Uncertain
0.47
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
.;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Benign
0.43
N
LIST_S2
Uncertain
0.95
D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.89
D;D
MetaSVM
Uncertain
-0.12
T
MutationAssessor
Pathogenic
4.0
.;H
MutationTaster
Benign
0.61
D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-7.3
D;D
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Vest4
0.78
MVP
0.38
ClinPred
0.99
D
GERP RS
3.3
Varity_R
0.78
gMVP
0.77

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.

Other links and lift over

dbSNP: rs1926055212; hg19: chr22-21900468; API