11-62666557-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001043229.2(CSKMT):ā€‹c.229C>Gā€‹(p.Leu77Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

CSKMT
NM_001043229.2 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00700
Variant links:
Genes affected
CSKMT (HGNC:33113): (citrate synthase lysine methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine dimethylation; peptidyl-lysine monomethylation; and peptidyl-lysine trimethylation. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]
LBHD1 (HGNC:28351): (LBH domain containing 1) This gene shares three exons in common with another gene, chromosome 11 open reading frame 98 (GeneID:102288414), but the encoded protein uses a reading frame that is different from that of the chromosome 11 open reading frame 98 gene. [provided by RefSeq, Nov 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.039260417).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CSKMTNM_001043229.2 linkuse as main transcriptc.229C>G p.Leu77Val missense_variant 3/3 ENST00000532971.2 NP_001036694.1 A8MUP2
LBHD1NM_024099.5 linkuse as main transcriptc.538+966G>C intron_variant ENST00000354588.8 NP_077004.2 Q9BQE6-2A0A024R584

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CSKMTENST00000532971.2 linkuse as main transcriptc.229C>G p.Leu77Val missense_variant 3/32 NM_001043229.2 ENSP00000431287.1 A8MUP2
LBHD1ENST00000354588.8 linkuse as main transcriptc.538+966G>C intron_variant 1 NM_024099.5 ENSP00000346600.3 Q9BQE6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461850
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727224
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:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsMay 20, 2024The c.229C>G (p.L77V) alteration is located in exon 3 (coding exon 2) of the METTL12 gene. This alteration results from a C to G substitution at nucleotide position 229, causing the leucine (L) at amino acid position 77 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
0.070
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
8.5
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0017
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.64
N
REVEL
Benign
0.069
Sift
Benign
0.12
T
Sift4G
Benign
0.18
T
Polyphen
0.0080
B
Vest4
0.035
MutPred
0.27
Loss of loop (P = 0.1242);
MVP
0.040
MPC
0.026
ClinPred
0.036
T
GERP RS
0.69
Varity_R
0.11
gMVP
0.28

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.

Other links and lift over

dbSNP: rs1370043836; hg19: chr11-62434029; API