12-8713870-T-C

Position:

• chr12-8713870-T-C

Variant summary

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

The NM_001297776.2(RIMKLB):​c.4T>C​(p.Cys2Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIMKLB NM_001297776.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26

Genes affected

RIMKLB (HGNC:29228): (ribosomal modification protein rimK like family member B) Predicted to enable N-acetyl-L-aspartate-L-glutamate ligase activity and citrate-L-glutamate ligase activity. Predicted to be involved in glutamine family amino acid metabolic process. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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
RIMKLB	NM_001297776.2	c.4T>C	p.Cys2Arg	missense_variant	2/6	ENST00000535829.6	NP_001284705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMKLB	ENST00000535829.6	c.4T>C	p.Cys2Arg	missense_variant	2/6	2	NM_001297776.2	ENSP00000445863	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 26, 2023

The c.4T>C (p.C2R) alteration is located in exon 3 (coding exon 1) of the RIMKLB gene. This alteration results from a T to C substitution at nucleotide position 4, causing the cysteine (C) at amino acid position 2 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	Benign	0.19
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;T;T;T;T;T;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.71	T;T;T;.;T;.;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.59	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.69	.;.;.;N;N;N;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.2	D;D;D;N;N;N;.
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D;D;T;T;T;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0, 1.0	.;.;.;D;D;D;D
Vest4		0.79, 0.79, 0.79, 0.79
MutPred		0.41		Gain of MoRF binding (P = 7e-04);Gain of MoRF binding (P = 7e-04);.;Gain of MoRF binding (P = 7e-04);Gain of MoRF binding (P = 7e-04);Gain of MoRF binding (P = 7e-04);Gain of MoRF binding (P = 7e-04);
MVP		0.20
MPC		2.5
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.57
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-8866466;