chr1-65230247-G-A

Variant names:

• chr1-65230247-G-A
• rs1336472
• NM_013410.4:c.*4070G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013410.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK4	NM_013410.4	MANE Select	c.*4070G>A		3_prime_UTR	Exon 5 of 5	NP_037542.1
	AK4	NM_001005353.3		c.*4070G>A		3_prime_UTR	Exon 6 of 6	NP_001005353.1
	AK4	NM_203464.3		c.*4070G>A		3_prime_UTR	Exon 6 of 6	NP_982289.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK4	ENST00000327299.8	TSL:1 MANE Select	c.*4070G>A		3_prime_UTR	Exon 5 of 5	ENSP00000322175.7
	AK4	ENST00000395334.6	TSL:1	c.*4070G>A		3_prime_UTR	Exon 6 of 6	ENSP00000378743.2
	AK4	ENST00000545314.5	TSL:1	c.*4070G>A		3_prime_UTR	Exon 6 of 6	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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 5 AN: 10

Other (OTH) AF: 0.500 AC: 3 AN: 6

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

African (AFR) AF: 0.889 AC: 36897 AN: 41486

American (AMR) AF: 0.588 AC: 8971 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1345 AN: 3468

East Asian (EAS) AF: 0.672 AC: 3457 AN: 5144

South Asian (SAS) AF: 0.513 AC: 2468 AN: 4810

European-Finnish (FIN) AF: 0.358 AC: 3771 AN: 10546

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26640 AN: 67962

Other (OTH) AF: 0.535 AC: 1129 AN: 2112

Alfa AF: 0.467 Hom.: 47355

Bravo AF: 0.592

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.48
PhyloP100		-1.3
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: rs1336472; hg19: chr1-65695930;