rs2799561

Variant names:

• chr1-77303805-T-C
• rs2799561
• NM_174858.3:c.699+5858T>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.699+5858T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,224 control chromosomes in the GnomAD database, including 2,207 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 (2207 hom., cov: 33)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.900
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.699+5858T>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.699+5858T>C		intron_variant	Intron 5 of 13	1	NM_174858.3	ENSP00000346577.2
AK5	ENST00000344720.9	c.621+5858T>C		intron_variant	Intron 5 of 13	1		ENSP00000341430.5
AK5	ENST00000317704.8	n.883+5858T>C		intron_variant	Intron 5 of 5	2
AK5	ENST00000524494.1	n.93+5858T>C		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23496 AN: 152106 Hom.: 2207 Cov.: 33

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.154 AC: 23499 AN: 152224 Hom.: 2207 Cov.: 33 AF XY: 0.157 AC XY: 11695 AN XY: 74414

African (AFR) AF: 0.0641 AC: 2663 AN: 41550

American (AMR) AF: 0.113 AC: 1730 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0825 AC: 286 AN: 3468

East Asian (EAS) AF: 0.148 AC: 764 AN: 5176

South Asian (SAS) AF: 0.104 AC: 504 AN: 4824

European-Finnish (FIN) AF: 0.299 AC: 3167 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13833 AN: 68006

Other (OTH) AF: 0.156 AC: 330 AN: 2114

Alfa AF: 0.185 Hom.: 563

Bravo AF: 0.139

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	-0.90
CADD	Benign	1.5
DANN	Benign	0.75
PhyloP100		0.90
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: rs2799561; hg19: chr1-77769490;