rs1336472

Positions:

• chr1-65230247-G-A
• chr1-65230247-G-T

Variant summary

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

The NM_013410.4(AK4):​c.*4070G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,014 control chromosomes in the GnomAD database, including 27,618 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 0.56 (27615 hom., cov: 32)
  • Exomes 𝑓: 0.50 (3 hom.)
• Consequence: AK4 NM_013410.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK4	NM_013410.4	c.*4070G>A		3_prime_UTR_variant	5/5	ENST00000327299.8	NP_037542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK4	ENST00000327299.8	c.*4070G>A		3_prime_UTR_variant	5/5	1	NM_013410.4	ENSP00000322175.7
AK4	ENST00000395334.6	c.*4070G>A		3_prime_UTR_variant	6/6	1		ENSP00000378743.2
AK4	ENST00000545314.5	c.*4070G>A		3_prime_UTR_variant	6/6	1		ENSP00000445912.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85074 AN: 151872 Hom.: 27550 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.587

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.500 AC: 11 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.450 AC XY: 9 AN XY: 20

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.561 AC: 85208 AN: 151992 Hom.: 27615 Cov.: 32 AF XY: 0.561 AC XY: 41679 AN XY: 74280

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.535

Alfa AF: 0.459 Hom.: 14214

Bravo AF: 0.592

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.48

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: rs1336472; hg19: chr1-65695930;