1-77361047-T-G

Variant names:

• chr1-77361047-T-G
• rs10493604
• NM_174858.3:c.891+20479T>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.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
• Publications: 4 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]

AK5-AS1 (HGNC:40069):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK5	NM_174858.3	MANE Select	c.891+20479T>G		intron	N/A	NP_777283.1	Q9Y6K8-1
	AK5	NM_012093.4		c.813+20479T>G		intron	N/A	NP_036225.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK5	ENST00000354567.7	TSL:1 MANE Select	c.891+20479T>G		intron	N/A	ENSP00000346577.2	Q9Y6K8-1
	AK5	ENST00000344720.9	TSL:1	c.813+20479T>G		intron	N/A	ENSP00000341430.5	Q9Y6K8-3
	AK5	ENST00000465146.5	TSL:3	n.164+20479T>G		intron	N/A

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

African (AFR) AF: 0.123 AC: 5121 AN: 41510

American (AMR) AF: 0.189 AC: 2885 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0827 AC: 287 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1900 AN: 5156

South Asian (SAS) AF: 0.182 AC: 877 AN: 4810

European-Finnish (FIN) AF: 0.0848 AC: 899 AN: 10602

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8328 AN: 68002

Other (OTH) AF: 0.147 AC: 311 AN: 2116

Alfa AF: 0.124 Hom.: 1613

Bravo AF: 0.145

Asia WGS AF: 0.229 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.0
DANN	Benign	0.66
PhyloP100		-0.073
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: rs10493604; hg19: chr1-77826732;