rs779457794

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001043229.2(CSKMT):​c.511C>G​(p.Arg171Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R171W) has been classified as Uncertain significance.

Frequency

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

Consequence

CSKMT
NM_001043229.2 missense

Scores

4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.120

Publications

1 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2915024).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSKMTNM_001043229.2 linkc.511C>G p.Arg171Gly missense_variant Exon 3 of 3 ENST00000532971.2 NP_001036694.1 A8MUP2
LBHD1NM_024099.5 linkc.538+684G>C 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.511C>G p.Arg171Gly missense_variant Exon 3 of 3 2 NM_001043229.2 ENSP00000431287.1 A8MUP2
LBHD1ENST00000354588.8 linkc.538+684G>C intron_variant Intron 4 of 6 1 NM_024099.5 ENSP00000346600.3 Q9BQE6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000401
AC:
1
AN:
249528
AF XY:
0.00000739
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461874
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727236
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:
0.0000116
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
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
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
19
DANN
Benign
0.86
DEOGEN2
Benign
0.0025
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.86
T
PhyloP100
0.12
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-2.4
N
REVEL
Uncertain
0.29
Sift
Uncertain
0.011
D
Sift4G
Uncertain
0.023
D
Polyphen
1.0
D
Vest4
0.37
MutPred
0.43
Loss of stability (P = 0.0439);
MVP
0.29
MPC
0.16
ClinPred
0.47
T
GERP RS
0.065
Varity_R
0.24
gMVP
0.47
Mutation Taster
=91/9
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs779457794; hg19: chr11-62434311; API