1-77361047-T-G

Position:

• chr1-77361047-T-G

Variant summary

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

The NM_174858.3(AK5):​c.891+20479T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,160 control chromosomes in the GnomAD database, including 1,652 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 0.14 (1652 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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]

AK5 (HGNC:):

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 = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK5	NM_174858.3	c.891+20479T>G		intron_variant		ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.891+20479T>G		intron_variant		1	NM_174858.3	ENSP00000346577.2
AK5	ENST00000344720.9	c.813+20479T>G		intron_variant		1		ENSP00000341430.5
AK5	ENST00000465146.5	n.164+20479T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20826 AN: 152042 Hom.: 1645 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0848

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.137 AC: 20828 AN: 152160 Hom.: 1652 Cov.: 32 AF XY: 0.137 AC XY: 10206 AN XY: 74400

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0848

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.147

Alfa AF: 0.120 Hom.: 1169

Bravo AF: 0.145

Asia WGS AF: 0.229 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.66

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: rs10493604; hg19: chr1-77826732;