Variant 11-62666596-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001043229.2(CSKMT):c.268T>C(p.Cys90Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

CSKMT
NM_001043229.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.46

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]

CSKMT links:

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]

LBHD1 links:

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ACMG classification

Classification made for transcript

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
CSKMT	NM_001043229.2 linkuse as main transcript	c.268T>C	p.Cys90Arg	missense_variant	3/3	ENST00000532971.2	NP_001036694.1
LBHD1	NM_024099.5 linkuse as main transcript	c.538+927A>G		intron_variant		ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSKMT	ENST00000532971.2 linkuse as main transcript	c.268T>C	p.Cys90Arg	missense_variant	3/3	2	NM_001043229.2	ENSP00000431287	P1
LBHD1	ENST00000354588.8 linkuse as main transcript	c.538+927A>G		intron_variant		1	NM_024099.5	ENSP00000346600	P1	Q9BQE6-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727232

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

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 submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.268T>C (p.C90R) alteration is located in exon 3 (coding exon 2) of the METTL12 gene. This alteration results from a T to C substitution at nucleotide position 268, causing the cysteine (C) at amino acid position 90 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0055

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.55

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.061

Sift4G

Benign

0.077

Polyphen

0.36

Vest4

0.63

MutPred

0.60

Gain of disorder (P = 0.0108);

MVP

0.39

MPC

0.17

ClinPred

0.43

GERP RS

2.0

Varity_R

0.65

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over