Variant chr12-130406233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001393629.1(RIMBP2):c.3704C>T(p.Thr1235Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000965 in 1,450,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

RIMBP2
NM_001393629.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50

Variant links:

Genes affected

RIMBP2 (HGNC:30339): (RIMS binding protein 2) Predicted to be involved in neuromuscular synaptic transmission. Predicted to be located in plasma membrane and synapse. Predicted to be active in presynaptic active zone cytoplasmic component. [provided by Alliance of Genome Resources, Apr 2022]

RIMBP2 links:

PIWIL1 (HGNC:):

PIWIL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP2	NM_001393629.1 linkuse as main transcript	c.3704C>T	p.Thr1235Ile	missense_variant	21/23	ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1 linkuse as main transcript	c.3704C>T	p.Thr1235Ile	missense_variant	21/23		NM_001393629.1	ENSP00000509157	P5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246940

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133380

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000965

AC:

AN:

1450350

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

721718

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000896

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.0000597

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

May 24, 2023

The c.2936C>T (p.T979I) alteration is located in exon 17 (coding exon 15) of the RIMBP2 gene. This alteration results from a C to T substitution at nucleotide position 2936, causing the threonine (T) at amino acid position 979 to be replaced by an isoleucine (I). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.031

MetaRNN

Uncertain

0.64

D;D

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-3.6

D;.

REVEL

Benign

0.28

Sift

Uncertain

0.015

D;.

Sift4G

Uncertain

0.025

D;.

Polyphen

0.49

P;.

Vest4

0.75

MutPred

0.63

Gain of catalytic residue at D984 (P = 6e-04);.;

MVP

0.61

MPC

0.63

ClinPred

0.89

GERP RS

4.3

Varity_R

0.29

gMVP

0.72

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