rs2438652

Variant names:

• chr5-10239149-G-A
• rs2438652
• NM_199133.4:c.224C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199133.4(ATPSCKMT):​c.224C>T​(p.Thr75Met) variant causes a missense change. The variant allele was found at a frequency of 0.179 in 1,613,942 control chromosomes in the GnomAD database, including 39,939 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (4105 hom., cov: 33)
  • Exomes 𝑓: 0.18 (35834 hom.)
• Consequence: ATPSCKMT NM_199133.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.12
• Publications: 25 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.826355E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	NM_199133.4	MANE Select	c.224C>T	p.Thr75Met	missense	Exon 2 of 5	NP_954584.2
	ATPSCKMT	NM_001258388.2		c.224C>T	p.Thr75Met	missense	Exon 2 of 4	NP_001245317.1
	ATPSCKMT	NM_001258389.2		c.224C>T	p.Thr75Met	missense	Exon 2 of 5	NP_001245318.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	ENST00000511437.6	TSL:1 MANE Select	c.224C>T	p.Thr75Met	missense	Exon 2 of 5	ENSP00000422338.1
	ATPSCKMT	ENST00000280330.12	TSL:2	c.-294C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000280330.8
	ATPSCKMT	ENST00000510047.5	TSL:2	c.224C>T	p.Thr75Met	missense	Exon 2 of 4	ENSP00000420876.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28853 AN: 151982 Hom.: 4097 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.259 AC: 64684 AN: 249522 AF XY: 0.250

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.465

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.770

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.140

Gnomad OTH exome AF: 0.229

GnomAD4 exome AF: 0.178 AC: 260668 AN: 1461842 Hom.: 35834 Cov.: 32 AF XY: 0.181 AC XY: 131676 AN XY: 727214

African (AFR) AF: 0.140 AC: 4685 AN: 33478

American (AMR) AF: 0.444 AC: 19840 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 5560 AN: 26136

East Asian (EAS) AF: 0.819 AC: 32498 AN: 39700

South Asian (SAS) AF: 0.305 AC: 26296 AN: 86246

European-Finnish (FIN) AF: 0.179 AC: 9536 AN: 53410

Middle Eastern (MID) AF: 0.235 AC: 1355 AN: 5768

European-Non Finnish (NFE) AF: 0.134 AC: 148686 AN: 1111994

Other (OTH) AF: 0.202 AC: 12212 AN: 60396

GnomAD4 genome AF: 0.190 AC: 28884 AN: 152100 Hom.: 4105 Cov.: 33 AF XY: 0.202 AC XY: 14987 AN XY: 74350

African (AFR) AF: 0.139 AC: 5786 AN: 41496

American (AMR) AF: 0.326 AC: 4985 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3988 AN: 5162

South Asian (SAS) AF: 0.317 AC: 1526 AN: 4814

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10568

Middle Eastern (MID) AF: 0.238 AC: 69 AN: 290

European-Non Finnish (NFE) AF: 0.139 AC: 9438 AN: 68000

Other (OTH) AF: 0.202 AC: 428 AN: 2114

Alfa AF: 0.170 Hom.: 15937

Bravo AF: 0.201

TwinsUK AF: 0.122 AC: 451

ALSPAC AF: 0.128 AC: 494

ESP6500AA AF: 0.127 AC: 519

ESP6500EA AF: 0.138 AC: 1149

ExAC AF: 0.246 AC: 29752

Asia WGS AF: 0.519 AC: 1800 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.1
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.14
Sift	Benign	0.063	T
Sift4G	Benign	0.082	T
Polyphen		0.076	B
Vest4		0.080
MPC		0.28
ClinPred		0.025	T
GERP RS		5.2
Varity_R		0.073
gMVP		0.52
Mutation Taster		=291/9	polymorphism (auto)

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: rs2438652; hg19: chr5-10239261; COSMIC: COSV54726828;