5-10247853-T-G

Variant names:

• chr5-10247853-T-G
• rs2548553
• NM_199133.4:c.16+2005A>C

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+2005A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 152,128 control chromosomes in the GnomAD database, including 43,426 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 0.74 (43426 hom., cov: 33)
• Consequence: ATPSCKMT NM_199133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 5 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 (BayesDel_noAF=-1.03).
• 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+2005A>C		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+2005A>C		intron_variant	Intron 1 of 4	1	NM_199133.4	ENSP00000422338.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111964 AN: 152010 Hom.: 43407 Cov.: 33

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.736 AC: 112025 AN: 152128 Hom.: 43426 Cov.: 33 AF XY: 0.739 AC XY: 54941 AN XY: 74374

African (AFR) AF: 0.467 AC: 19333 AN: 41424

American (AMR) AF: 0.809 AC: 12368 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3058 AN: 3470

East Asian (EAS) AF: 0.863 AC: 4472 AN: 5180

South Asian (SAS) AF: 0.648 AC: 3124 AN: 4824

European-Finnish (FIN) AF: 0.844 AC: 8947 AN: 10596

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.854 AC: 58101 AN: 68020

Other (OTH) AF: 0.766 AC: 1621 AN: 2116

Alfa AF: 0.776 Hom.: 8292

Bravo AF: 0.726

Asia WGS AF: 0.762 AC: 2649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.47
PhyloP100		-0.65
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: rs2548553; hg19: chr5-10247965;