Genetic Variant CSKMT:p.Arg171Leu (chr11-62666840-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001043229.2(CSKMT):c.512G>T(p.Arg171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R171P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CSKMT
NM_001043229.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

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]

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 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=0.35532886).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001043229.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSKMT	NM_001043229.2	MANE Select	c.512G>T	p.Arg171Leu	missense	Exon 3 of 3	NP_001036694.1	A8MUP2
LBHD1	NM_024099.5	MANE Select	c.538+683C>A		intron	N/A	NP_077004.2
LBHD1	NM_001394599.1		c.1030+683C>A		intron	N/A	NP_001381528.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CSKMT	ENST00000532971.2	TSL:2 MANE Select	c.512G>T	p.Arg171Leu	missense	Exon 3 of 3	ENSP00000431287.1	A8MUP2
LBHD1	ENST00000354588.8	TSL:1 MANE Select	c.538+683C>A		intron	N/A	ENSP00000346600.3	Q9BQE6-2
CSKMT	ENST00000529868.1	TSL:1	n.1214G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249518

AF XY:

0.00

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ExAC

AF:

0.00000827

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0030

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.73

M_CAP

Benign

0.031

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.93

PhyloP100

1.9

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

REVEL

Benign

0.25

Sift

Uncertain

0.013

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.41

MutPred

0.38

Loss of MoRF binding (P = 0.1797)

MVP

0.37

MPC

0.14

ClinPred

0.73

GERP RS

1.8

Varity_R

0.17

gMVP

0.50

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over