rs2815324

Variant names:

• chr1-77326004-T-C
• rs2815324
• NM_174858.3:c.700-14373T>C

Variant summary

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

The NM_174858.3(AK5):​c.700-14373T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,162 control chromosomes in the GnomAD database, including 2,234 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 0.15 (2234 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 6 publications found

Genes affected

AK5 (HGNC:365): (adenylate kinase 5) This gene encodes a member of the adenylate kinase family, which is involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. This member is related to the UMP/CMP kinase of several species. It is located in the cytosol and expressed exclusively in brain. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.700-14373T>C		intron_variant	Intron 5 of 13	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.700-14373T>C		intron_variant	Intron 5 of 13	1	NM_174858.3	ENSP00000346577.2
AK5	ENST00000344720.9	c.622-14373T>C		intron_variant	Intron 5 of 13	1		ENSP00000341430.5
AK5	ENST00000524494.1	n.94-14373T>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23191 AN: 152044 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.152 AC: 23177 AN: 152162 Hom.: 2234 Cov.: 32 AF XY: 0.154 AC XY: 11489 AN XY: 74384

African (AFR) AF: 0.0503 AC: 2090 AN: 41522

American (AMR) AF: 0.114 AC: 1737 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.147 AC: 761 AN: 5184

South Asian (SAS) AF: 0.108 AC: 519 AN: 4816

European-Finnish (FIN) AF: 0.300 AC: 3166 AN: 10560

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14033 AN: 67996

Other (OTH) AF: 0.150 AC: 317 AN: 2108

Alfa AF: 0.130 Hom.: 663

Bravo AF: 0.136

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.74
PhyloP100		0.44
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: rs2815324; hg19: chr1-77791689;