12-130437119-G-T

Variant names:

• chr12-130437119-G-T
• rs2292664
• NM_001393629.1:c.1829C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001393629.1(RIMBP2):​c.1829C>A​(p.Pro610Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RIMBP2 NM_001393629.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32992262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIMBP2	NM_001393629.1	c.1829C>A	p.Pro610Gln	missense_variant	Exon 13 of 23	ENST00000690449.1	NP_001380558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIMBP2	ENST00000690449.1	c.1829C>A	p.Pro610Gln	missense_variant	Exon 13 of 23		NM_001393629.1	ENSP00000509157.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431902 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 708382

African (AFR) AF: 0.00 AC: 0 AN: 32890

American (AMR) AF: 0.00 AC: 0 AN: 41752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24328

East Asian (EAS) AF: 0.00 AC: 0 AN: 38958

South Asian (SAS) AF: 0.00 AC: 0 AN: 82110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095514

Other (OTH) AF: 0.00 AC: 0 AN: 58996

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.057
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	2.9	M;.;.
PhyloP100		2.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.4	D;.;.
REVEL	Benign	0.17
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.041	D;.;.
Vest4		0.34
ClinPred		0.98	D
GERP RS		2.6
Varity_R		0.27
gMVP		0.40
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs2292664; hg19: chr12-130921664;