1-77297857-A-G

Position:

• chr1-77297857-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP3_Moderate BP7 BS1 BS2

The NM_174858.3(AK5):​c.609A>G​(p.Lys203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,612,672 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (55 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (44 hom.)
• Consequence: AK5 NM_174858.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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 -7 ACMG points.

• PP3: BayesDel_noAF computational evidence supports a deleterious effect, 0.35
• BP7: Synonymous conserved (PhyloP=1.94 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0145 (2204/152326) while in subpopulation AFR AF= 0.0503 (2090/41584). AF 95% confidence interval is 0.0485. There are 55 homozygotes in gnomad4. There are 1040 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK5	NM_174858.3	c.609A>G	p.Lys203=	synonymous_variant	5/14	ENST00000354567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK5	ENST00000354567.7	c.609A>G	p.Lys203=	synonymous_variant	5/14	1	NM_174858.3	P1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2196 AN: 152208 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00137 AC: 2000 AN: 1460346 Hom.: 44 Cov.: 30 AF XY: 0.00118 AC XY: 856 AN XY: 726310

Gnomad4 AFR exome AF: 0.0488

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000701

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000666

Gnomad4 OTH exome AF: 0.00290

GnomAD4 genome AF: 0.0145 AC: 2204 AN: 152326 Hom.: 55 Cov.: 33 AF XY: 0.0140 AC XY: 1040 AN XY: 74490

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00661 Hom.: 13

Bravo AF: 0.0156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.35
CADD	Benign	7.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1167206; hg19: chr1-77763542;