1-77402139-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174858.3(AK5):c.892-8842C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,144 control chromosomes in the GnomAD database, including 893 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 0.099 (893 hom., cov: 32)
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK5	NM_174858.3	c.892-8842C>G		intron_variant		ENST00000354567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK5	ENST00000354567.7	c.892-8842C>G		intron_variant		1	NM_174858.3	P1
AK5	ENST00000344720.9	c.814-8842C>G		intron_variant		1
AK5	ENST00000465146.5	n.165-8842C>G		intron_variant, non_coding_transcript_variant		3
AK5	ENST00000530826.1	n.91-8842C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14943 AN: 152026 Hom.: 879 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.0986 AC: 15000 AN: 152144 Hom.: 893 Cov.: 32 AF XY: 0.0981 AC XY: 7299 AN XY: 74394

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0929

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0335 Hom.: 30

Bravo AF: 0.103

Asia WGS AF: 0.200 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.4
Dann	Benign	0.78

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: rs17098286; hg19: chr1-77867824;