NM_013410.4:c.145+19262T>C

Variant names:

• chr1-65167814-T-C
• rs1109374
• NM_013410.4:c.145+19262T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013410.4(AK4):​c.145+19262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,014 control chromosomes in the GnomAD database, including 6,059 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 0.27 (6059 hom., cov: 32)
• Consequence: AK4 NM_013410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963
• Publications: 5 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK4	NM_013410.4	c.145+19262T>C		intron_variant	Intron 1 of 4	ENST00000327299.8	NP_037542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK4	ENST00000327299.8	c.145+19262T>C		intron_variant	Intron 1 of 4	1	NM_013410.4	ENSP00000322175.7

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41418 AN: 151896 Hom.: 6056 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.273 AC: 41440 AN: 152014 Hom.: 6059 Cov.: 32 AF XY: 0.273 AC XY: 20319 AN XY: 74318

African (AFR) AF: 0.322 AC: 13350 AN: 41446

American (AMR) AF: 0.228 AC: 3476 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 831 AN: 3468

East Asian (EAS) AF: 0.574 AC: 2963 AN: 5158

South Asian (SAS) AF: 0.189 AC: 913 AN: 4818

European-Finnish (FIN) AF: 0.254 AC: 2681 AN: 10552

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16302 AN: 67986

Other (OTH) AF: 0.264 AC: 558 AN: 2112

Alfa AF: 0.245 Hom.: 10624

Bravo AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-0.96
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: rs1109374; hg19: chr1-65633497;