GeneBe

11-62666503-G-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001043229.2(CSKMT):​c.175G>T​(p.Glu59*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CSKMT
NM_001043229.2 stop_gained

Scores

2
3
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSKMTNM_001043229.2 linkc.175G>T p.Glu59* stop_gained Exon 3 of 3 ENST00000532971.2 NP_001036694.1 A8MUP2
LBHD1NM_024099.5 linkc.538+1020C>A intron_variant Intron 4 of 6 ENST00000354588.8 NP_077004.2 Q9BQE6-2A0A024R584

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSKMTENST00000532971.2 linkc.175G>T p.Glu59* stop_gained Exon 3 of 3 2 NM_001043229.2 ENSP00000431287.1 A8MUP2
LBHD1ENST00000354588.8 linkc.538+1020C>A intron_variant Intron 4 of 6 1 NM_024099.5 ENSP00000346600.3 Q9BQE6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461800
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727206
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53328
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1112010
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
36
DANN
Uncertain
1.0
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.42
N
PhyloP100
0.68
Vest4
0.022
GERP RS
3.6
Mutation Taster
=107/93
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

Publications

Other links and lift over

dbSNP: rs375107020; hg19: chr11-62433975; COSMIC: COSV63473147; COSMIC: COSV63473147; API