1-77419597-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.1059+1882A>G		intron_variant	Intron 8 of 13	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.1059+1882A>G		intron_variant	Intron 8 of 13	1	NM_174858.3	ENSP00000346577.2
AK5	ENST00000344720.9	c.981+1882A>G		intron_variant	Intron 8 of 13	1		ENSP00000341430.5
AK5	ENST00000527263.1	n.21+1882A>G		intron_variant	Intron 1 of 5	3		ENSP00000436859.1
AK5	ENST00000530826.1	n.258+1882A>G		intron_variant	Intron 3 of 7	3

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

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.942

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.881

Gnomad4 FIN AF: 0.872

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.888

Alfa AF: 0.923 Hom.: 86325

Bravo AF: 0.917

Asia WGS AF: 0.799 AC: 2779 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.7
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs9633478; hg19: chr1-77885282;