rs4702684

chr5-10245823-A-Cchr5-10245823-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
ATPSCKMT	NM_199133.4	c.16+4035T>G		intron_variant		ENST00000511437.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATPSCKMT	ENST00000511437.6	c.16+4035T>G		intron_variant		1	NM_199133.4	P1

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

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.361

Alfa AF: 0.341 Hom.: 2498

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4702684; hg19: chr5-10245935;