1-77419597-A-G

Variant names:

• chr1-77419597-A-G
• rs9633478
• NM_174858.3:c.1059+1882A>G

Variant summary

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

The NM_174858.3(AK5):​c.1059+1882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 152,186 control chromosomes in the GnomAD database, including 63,223 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 0.91 (63223 hom., cov: 31)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174858.3. 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
	AK5	NM_174858.3	MANE Select	c.1059+1882A>G		intron	N/A	NP_777283.1
	AK5	NM_012093.4		c.981+1882A>G		intron	N/A	NP_036225.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK5	ENST00000354567.7	TSL:1 MANE Select	c.1059+1882A>G		intron	N/A	ENSP00000346577.2
	AK5	ENST00000344720.9	TSL:1	c.981+1882A>G		intron	N/A	ENSP00000341430.5
	AK5	ENST00000527263.1	TSL:3	n.21+1882A>G		intron	N/A	ENSP00000436859.1

Frequencies

GnomAD3 genomes AF: 0.911 AC: 138524 AN: 152068 Hom.: 63181 Cov.: 31

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.872

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.911 AC: 138620 AN: 152186 Hom.: 63223 Cov.: 31 AF XY: 0.908 AC XY: 67561 AN XY: 74402

African (AFR) AF: 0.904 AC: 37519 AN: 41514

American (AMR) AF: 0.942 AC: 14400 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3118 AN: 3470

East Asian (EAS) AF: 0.812 AC: 4205 AN: 5180

South Asian (SAS) AF: 0.881 AC: 4245 AN: 4820

European-Finnish (FIN) AF: 0.872 AC: 9224 AN: 10582

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62874 AN: 68018

Other (OTH) AF: 0.888 AC: 1880 AN: 2116

Alfa AF: 0.923 Hom.: 108232

Bravo AF: 0.917

Asia WGS AF: 0.799 AC: 2779 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		0.084
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: rs9633478; hg19: chr1-77885282;