1-42381055-C-G

Position:

• chr1-42381055-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173642.4(RIMKLA):​c.121C>G​(p.Leu41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,162,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: RIMKLA NM_173642.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.958

Genes affected

RIMKLA (HGNC:28725): (ribosomal modification protein rimK like family member A) Predicted to enable N-acetyl-L-aspartate-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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08147848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIMKLA	NM_173642.4	c.121C>G	p.Leu41Val	missense_variant	1/5	ENST00000431473.4	NP_775913.2
RIMKLA	XM_006710585.4	c.121C>G	p.Leu41Val	missense_variant	1/5		XP_006710648.1
RIMKLA	XM_047418484.1	c.-313C>G		5_prime_UTR_variant	1/6		XP_047274440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIMKLA	ENST00000431473.4	c.121C>G	p.Leu41Val	missense_variant	1/5	1	NM_173642.4	ENSP00000414330	P1
RIMKLA	ENST00000410070.6	c.-313C>G		5_prime_UTR_variant	1/5	3		ENSP00000387064

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000258 AC: 3 AN: 1162530 Hom.: 0 Cov.: 29 AF XY: 0.00000536 AC XY: 3 AN XY: 559950

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000615

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000445

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3476

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

Aug 02, 2022

The c.121C>G (p.L41V) alteration is located in exon 1 (coding exon 1) of the RIMKLA gene. This alteration results from a C to G substitution at nucleotide position 121, causing the leucine (L) at amino acid position 41 to be replaced by a valine (V). 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	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.11	N
MutationTaster	Benign	0.88	D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.17
Sift	Benign	0.62	T
Sift4G	Benign	0.12	T
Polyphen		0.0050	B
Vest4		0.093
MutPred		0.42		Gain of MoRF binding (P = 0.1861);
MVP		0.014
MPC		0.45
ClinPred		0.15	T
GERP RS		3.6
Varity_R		0.082
gMVP		0.34

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

Other links and lift over

dbSNP: rs1451188363; hg19: chr1-42846726;