12-130422549-G-A

Position:

• chr12-130422549-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001393629.1(RIMBP2):​c.3142C>T​(p.Pro1048Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIMBP2 NM_001393629.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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]

PIWIL1 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052630782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMBP2	NM_001393629.1	c.3142C>T	p.Pro1048Ser	missense_variant	17/23	ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1	c.3142C>T	p.Pro1048Ser	missense_variant	17/23		NM_001393629.1	ENSP00000509157.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

The c.2374C>T (p.P792S) alteration is located in exon 13 (coding exon 11) of the RIMBP2 gene. This alteration results from a C to T substitution at nucleotide position 2374, causing the proline (P) at amino acid position 792 to be replaced by a serine (S). 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	0.077
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.041	T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N;.
REVEL	Benign	0.059
Sift	Benign	0.51	T;.
Sift4G	Benign	0.26	T;.
Polyphen		0.0010	B;.
Vest4		0.26
MutPred		0.29		Gain of catalytic residue at A795 (P = 0.0028);.;
MVP		0.26
MPC		0.28
ClinPred		0.11	T
GERP RS		1.9
Varity_R		0.028
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-130907094;