1-65212250-C-T

Position:

• chr1-65212250-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013410.4(AK4):​c.266-6504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,828 control chromosomes in the GnomAD database, including 12,214 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 0.39 (12214 hom., cov: 31)
• Consequence: AK4 NM_013410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

Genes affected

AK4 (HGNC:363): (adenylate kinase 4) This gene encodes a member of the adenylate kinase family of enzymes. The encoded protein is localized to the mitochondrial matrix. Adenylate kinases regulate the adenine and guanine nucleotide compositions within a cell by catalyzing the reversible transfer of phosphate group among these nucleotides. Five isozymes of adenylate kinase have been identified in vertebrates. Expression of these isozymes is tissue-specific and developmentally regulated. A pseudogene for this gene has been located on chromosome 17. Three transcript variants encoding the same protein have been identified for this gene. Sequence alignment suggests that the gene defined by NM_013410, NM_203464, and NM_001005353 is located on chromosome 1. [provided by RefSeq, Jul 2008]

AK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK4	NM_013410.4	c.266-6504C>T		intron_variant		ENST00000327299.8	NP_037542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK4	ENST00000327299.8	c.266-6504C>T		intron_variant		1	NM_013410.4	ENSP00000322175.7

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59721 AN: 151718 Hom.: 12200 Cov.: 31

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.383

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

GnomAD4 genome AF: 0.394 AC: 59779 AN: 151828 Hom.: 12214 Cov.: 31 AF XY: 0.397 AC XY: 29419 AN XY: 74170

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.388

Alfa AF: 0.340 Hom.: 12102

Bravo AF: 0.413

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.61

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: rs10789176; hg19: chr1-65677933; COSMIC: COSV59199509;