5-10245823-A-C

Variant names:

• chr5-10245823-A-C
• rs4702684
• NM_199133.4:c.16+4035T>G

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+4035T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,874 control chromosomes in the GnomAD database, including 10,086 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 0.35 (10086 hom., cov: 31)
• Consequence: ATPSCKMT NM_199133.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATPSCKMT	NM_199133.4	c.16+4035T>G		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+4035T>G		intron_variant	Intron 1 of 4	1	NM_199133.4	ENSP00000422338.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52639 AN: 151756 Hom.: 10060 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.347 AC: 52719 AN: 151874 Hom.: 10086 Cov.: 31 AF XY: 0.354 AC XY: 26272 AN XY: 74192

African (AFR) AF: 0.300 AC: 12409 AN: 41408

American (AMR) AF: 0.509 AC: 7756 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3468

East Asian (EAS) AF: 0.726 AC: 3756 AN: 5172

South Asian (SAS) AF: 0.452 AC: 2174 AN: 4812

European-Finnish (FIN) AF: 0.303 AC: 3182 AN: 10502

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21299 AN: 67954

Other (OTH) AF: 0.361 AC: 760 AN: 2106

Alfa AF: 0.353 Hom.: 4479

Bravo AF: 0.361

Asia WGS AF: 0.562 AC: 1954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.7
DANN	Benign	0.73
PhyloP100		0.36
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: rs4702684; hg19: chr5-10245935;