NM_199133.4:c.464C>T

Variant names:

• chr5-10235242-G-A
• rs369357904
• NM_199133.4:c.464C>T

Variant summary

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

The NM_199133.4(ATPSCKMT):​c.464C>T​(p.Ser155Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ATPSCKMT NM_199133.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.79
• Publications: 1 publications found

Genes affected

ATPSCKMT (HGNC:27029): (ATP synthase c subunit lysine N-methyltransferase) Enables protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine trimethylation; positive regulation of sensory perception of pain; and regulation of proton transport. Located in mitochondrial crista. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199133.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	NM_199133.4	MANE Select	c.464C>T	p.Ser155Leu	missense	Exon 4 of 5	NP_954584.2	Q6P4H8-1
	ATPSCKMT	NM_001258389.2		c.420C>T	p.Leu140Leu	synonymous	Exon 4 of 5	NP_001245318.1
	ATPSCKMT	NM_001258388.2		c.444+1236C>T		intron	N/A	NP_001245317.1	Q6P4H8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	ENST00000511437.6	TSL:1 MANE Select	c.464C>T	p.Ser155Leu	missense	Exon 4 of 5	ENSP00000422338.1	Q6P4H8-1
	ATPSCKMT	ENST00000280330.12	TSL:2	c.-29C>T		5_prime_UTR_premature_start_codon_gain	Exon 5 of 6	ENSP00000280330.8	J3KN90
	ATPSCKMT	ENST00000932928.1		c.464C>T	p.Ser155Leu	missense	Exon 4 of 5	ENSP00000602987.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248574 AF XY: 0.0000148

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: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461240 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726912

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111600

Other (OTH) AF: 0.00 AC: 0 AN: 60350

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000286652), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000120 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.18
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-1.0	T
PhyloP100		5.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.16
Sift	Benign	0.087	T
Sift4G	Benign	0.15	T
Polyphen		0.51	P
Vest4		0.61
MVP		0.24
MPC		0.21
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.18
gMVP		0.63
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs369357904; hg19: chr5-10235354;