5-10227599-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM4 BP6_Moderate BS2

The NM_199133.4(ATPSCKMT):c.544C>T(p.Arg182Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,614,160 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (20 hom.)
• Consequence: ATPSCKMT NM_199133.4 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.653

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM4: Stoplost variant in NM_199133.4 Downstream stopcodon found after 68 codons.
• BP6: Variant 5-10227599-G-A is Benign according to our data. Variant chr5-10227599-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATPSCKMT	NM_199133.4	c.544C>T	p.Arg182Ter	stop_gained	5/5	ENST00000511437.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATPSCKMT	ENST00000511437.6	c.544C>T	p.Arg182Ter	stop_gained	5/5	1	NM_199133.4	P1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 511 AN: 152154 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00934

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00460

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00339 AC: 846 AN: 249532 Hom.: 2 AF XY: 0.00339 AC XY: 459 AN XY: 135394

Gnomad AFR exome AF: 0.00116

Gnomad AMR exome AF: 0.000782

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00928

Gnomad NFE exome AF: 0.00508

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00389 AC: 5683 AN: 1461888 Hom.: 20 Cov.: 35 AF XY: 0.00379 AC XY: 2758 AN XY: 727244

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.000918

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00844

Gnomad4 NFE exome AF: 0.00445

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.00336 AC: 511 AN: 152272 Hom.: 3 Cov.: 33 AF XY: 0.00325 AC XY: 242 AN XY: 74446

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00934

Gnomad4 NFE AF: 0.00460

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00389 Hom.: 2

Bravo AF: 0.00276

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.00102 AC: 4

ESP6500EA AF: 0.00505 AC: 42

ExAC AF: 0.00376 AC: 455

EpiCase AF: 0.00409

EpiControl AF: 0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

ATPSCKMT: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.060
Cadd	Pathogenic	35
Dann	Benign	0.92
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.36	N
MutationTaster	Benign	1.0	D;D;D
Vest4		0.17
GERP RS		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200658616; hg19: chr5-10227711; COSMIC: COSV104600219; COSMIC: COSV104600219;