1-77558660-CTAT-CTATTATAT

Variant names:

• chr1-77558660-C-CTATTA
• rs6485
• NM_174858.3:c.1683_1684insATATT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_174858.3(AK5):​c.1683_1684insATATT​(p.Phe562IlefsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,730 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AK5 NM_174858.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1683_1684insATATT	p.Phe562IlefsTer24	frameshift	Exon 14 of 14	NP_777283.1	Q9Y6K8-1
	AK5	NM_012093.4		c.1605_1606insATATT	p.Phe536IlefsTer24	frameshift	Exon 14 of 14	NP_036225.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK5	ENST00000354567.7	TSL:1 MANE Select	c.1683_1684insATATT	p.Phe562IlefsTer24	frameshift	Exon 14 of 14	ENSP00000346577.2	Q9Y6K8-1
	AK5	ENST00000344720.9	TSL:1	c.1605_1606insATATT	p.Phe536IlefsTer24	frameshift	Exon 14 of 14	ENSP00000341430.5	Q9Y6K8-3
	AK5	ENST00000478255.1	TSL:2	c.228_229insATATT	p.Phe77IlefsTer24	frameshift	Exon 3 of 3	ENSP00000433915.1	E9PIS7

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440730 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 718248

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33308

American (AMR) AF: 0.00 AC: 0 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26032

East Asian (EAS) AF: 0.00 AC: 0 AN: 39586

South Asian (SAS) AF: 0.00 AC: 0 AN: 85644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092888

Other (OTH) AF: 0.0000168 AC: 1 AN: 59670

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs6485; hg19: chr1-78024345;