rs2578619

Variant names:

• chr5-10248685-C-T
• rs2578619
• NM_199133.4:c.16+1173G>A

Variant summary

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

The NM_199133.4(ATPSCKMT):​c.16+1173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,202 control chromosomes in the GnomAD database, including 43,349 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 0.73 (43349 hom., cov: 33)
• Consequence: ATPSCKMT NM_199133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.742
• Publications: 6 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]

ENSG00000248968 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPSCKMT	NM_199133.4	c.16+1173G>A		intron_variant	Intron 1 of 4	ENST00000511437.6	NP_954584.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATPSCKMT	ENST00000511437.6	c.16+1173G>A		intron_variant	Intron 1 of 4	1	NM_199133.4	ENSP00000422338.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111805 AN: 152084 Hom.: 43333 Cov.: 33

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.762

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.735 AC: 111863 AN: 152202 Hom.: 43349 Cov.: 33 AF XY: 0.738 AC XY: 54879 AN XY: 74412

African (AFR) AF: 0.462 AC: 19158 AN: 41482

American (AMR) AF: 0.808 AC: 12358 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3060 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4477 AN: 5188

South Asian (SAS) AF: 0.649 AC: 3126 AN: 4820

European-Finnish (FIN) AF: 0.845 AC: 8951 AN: 10588

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58115 AN: 68038

Other (OTH) AF: 0.762 AC: 1613 AN: 2116

Alfa AF: 0.775 Hom.: 8276

Bravo AF: 0.725

Asia WGS AF: 0.759 AC: 2638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.60
PhyloP100		0.74
Mutation Taster		=100/0	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: rs2578619; hg19: chr5-10248797;