11-62666509-C-T

Variant names:

• chr11-62666509-C-T
• rs372150390
• NM_001043229.2:c.181C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001043229.2(CSKMT):​c.181C>T​(p.Gln61*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,614,122 control chromosomes in the GnomAD database, including 32 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (29 hom.)
• Consequence: CSKMT NM_001043229.2 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.384
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-62666509-C-T is Benign according to our data. Variant chr11-62666509-C-T is described in ClinVar as [Benign]. Clinvar id is 726523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.00108 (1579/1461808) while in subpopulation SAS AF = 0.017 (1464/86258). AF 95% confidence interval is 0.0162. There are 29 homozygotes in GnomAdExome4. There are 1137 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSKMT	NM_001043229.2	c.181C>T	p.Gln61*	stop_gained	Exon 3 of 3	ENST00000532971.2	NP_001036694.1
LBHD1	NM_024099.5	c.538+1014G>A		intron_variant	Intron 4 of 6	ENST00000354588.8	NP_077004.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSKMT	ENST00000532971.2	c.181C>T	p.Gln61*	stop_gained	Exon 3 of 3	2	NM_001043229.2	ENSP00000431287.1
LBHD1	ENST00000354588.8	c.538+1014G>A		intron_variant	Intron 4 of 6	1	NM_024099.5	ENSP00000346600.3

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152196 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00225 AC: 562 AN: 249410 AF XY: 0.00301

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.00108 AC: 1579 AN: 1461808 Hom.: 29 Cov.: 32 AF XY: 0.00156 AC XY: 1137 AN XY: 727208

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0170 AC: 1464 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1112012

Other (OTH) AF: 0.00147 AC: 89 AN: 60396

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152314 Hom.: 3 Cov.: 32 AF XY: 0.000899 AC XY: 67 AN XY: 74486

African (AFR) AF: 0.0000240 AC: 1 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000152 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.00235 AC: 284

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Uncertain	0.34
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.30	N
PhyloP100		0.38
Vest4		0.017
GERP RS		3.6
Mutation Taster		=172/28	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

Other links and lift over

dbSNP: rs372150390; hg19: chr11-62433981; COSMIC: COSV63473610; COSMIC: COSV63473610;