22-21547058-G-T

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

1
18

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]

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
RIMBP3CNM_001128633.2 linkuse as main transcriptc.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
RIMBP3CENST00000433039.2 linkuse as main transcriptc.3919C>A p.Pro1307Thr missense_variant 1/1 NM_001128633.2 ENSP00000390630 P1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
0
Hom.:
0
Cov.:
0
FAILED QC
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.578
AC:
26611
AN:
46062
Hom.:
6166
Cov.:
0
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:
0
AN:
0
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
0
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 submitterclinical testingAmbry GeneticsApr 27, 2022The 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
T
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
N
LIST_S2
Benign
0.41
T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.061
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.25
T
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
T
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.

Other links and lift over

dbSNP: rs2242314; hg19: chr22-21901347; API