5-10239881-A-G

Variant names:

• chr5-10239881-A-G
• rs2445871
• NM_199133.4:c.17-525T>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.17-525T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,186 control chromosomes in the GnomAD database, including 3,361 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 0.16 (3361 hom., cov: 32)
• Consequence: ATPSCKMT NM_199133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	NM_199133.4	MANE Select	c.17-525T>C		intron	N/A	NP_954584.2	Q6P4H8-1
	ATPSCKMT	NM_001258388.2		c.17-525T>C		intron	N/A	NP_001245317.1	Q6P4H8-2
	ATPSCKMT	NM_001258389.2		c.17-525T>C		intron	N/A	NP_001245318.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATPSCKMT	ENST00000511437.6	TSL:1 MANE Select	c.17-525T>C		intron	N/A	ENSP00000422338.1	Q6P4H8-1
	ATPSCKMT	ENST00000932928.1		c.17-525T>C		intron	N/A	ENSP00000602987.1
	ATPSCKMT	ENST00000510047.5	TSL:2	c.17-525T>C		intron	N/A	ENSP00000420876.1	Q6P4H8-2

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23633 AN: 152068 Hom.: 3359 Cov.: 32

Gnomad AFR AF: 0.0681

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.155 AC: 23648 AN: 152186 Hom.: 3361 Cov.: 32 AF XY: 0.168 AC XY: 12466 AN XY: 74394

African (AFR) AF: 0.0682 AC: 2835 AN: 41548

American (AMR) AF: 0.308 AC: 4708 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3898 AN: 5170

South Asian (SAS) AF: 0.306 AC: 1474 AN: 4820

European-Finnish (FIN) AF: 0.157 AC: 1663 AN: 10568

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8081 AN: 68006

Other (OTH) AF: 0.171 AC: 361 AN: 2114

Alfa AF: 0.136 Hom.: 2815

Bravo AF: 0.164

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2445871; hg19: chr5-10239993;