1-77558660-CTAT-CTATTAT

Variant names:

• chr1-77558660-C-CTAT
• rs6485
• NM_174858.3:c.1681_1683dupATT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 1P and 10B. PM4_Supporting BP6_Moderate BA1

The NM_174858.3(AK5):​c.1681_1683dupATT​(p.Ile561dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,588,160 control chromosomes in the GnomAD database, including 447,473 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (34286 hom., cov: 0)
  • Exomes 𝑓: 0.75 (413187 hom.)
• Consequence: AK5 NM_174858.3 conservative_inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19
• Publications: 8 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: Benign. The variant received -9 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_174858.3. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 1-77558660-C-CTAT is Benign according to our data. Variant chr1-77558660-C-CTAT is described in ClinVar as Benign. ClinVar VariationId is 402359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.767 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.1681_1683dupATT	p.Ile561dup	conservative_inframe_insertion	Exon 14 of 14	NP_777283.1	Q9Y6K8-1
	AK5	NM_012093.4		c.1603_1605dupATT	p.Ile535dup	conservative_inframe_insertion	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.1681_1683dupATT	p.Ile561dup	conservative_inframe_insertion	Exon 14 of 14	ENSP00000346577.2	Q9Y6K8-1
	AK5	ENST00000344720.9	TSL:1	c.1603_1605dupATT	p.Ile535dup	conservative_inframe_insertion	Exon 14 of 14	ENSP00000341430.5	Q9Y6K8-3
	AK5	ENST00000478255.1	TSL:2	c.226_228dupATT	p.Ile76dup	conservative_inframe_insertion	Exon 3 of 3	ENSP00000433915.1	E9PIS7

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98893 AN: 151610 Hom.: 34285 Cov.: 0

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.648

GnomAD2 exomes AF: 0.723 AC: 180057 AN: 249188 AF XY: 0.722

Gnomad AFR exome AF: 0.391

Gnomad AMR exome AF: 0.834

Gnomad ASJ exome AF: 0.591

Gnomad EAS exome AF: 0.745

Gnomad FIN exome AF: 0.697

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.700

GnomAD4 exome AF: 0.753 AC: 1081596 AN: 1436430 Hom.: 413187 Cov.: 27 AF XY: 0.750 AC XY: 537501 AN XY: 716276

African (AFR) AF: 0.387 AC: 12828 AN: 33178

American (AMR) AF: 0.825 AC: 36680 AN: 44446

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 15328 AN: 25976

East Asian (EAS) AF: 0.723 AC: 28571 AN: 39542

South Asian (SAS) AF: 0.664 AC: 56762 AN: 85430

European-Finnish (FIN) AF: 0.698 AC: 37245 AN: 53372

Middle Eastern (MID) AF: 0.609 AC: 3474 AN: 5706

European-Non Finnish (NFE) AF: 0.779 AC: 848113 AN: 1089298

Other (OTH) AF: 0.716 AC: 42595 AN: 59482

GnomAD4 genome AF: 0.652 AC: 98915 AN: 151730 Hom.: 34286 Cov.: 0 AF XY: 0.648 AC XY: 48024 AN XY: 74112

African (AFR) AF: 0.399 AC: 16497 AN: 41366

American (AMR) AF: 0.759 AC: 11577 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.599 AC: 2076 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3795 AN: 5152

South Asian (SAS) AF: 0.658 AC: 3155 AN: 4792

European-Finnish (FIN) AF: 0.688 AC: 7214 AN: 10484

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52441 AN: 67896

Other (OTH) AF: 0.644 AC: 1357 AN: 2108

Alfa AF: 0.685 Hom.: 6248

Bravo AF: 0.645

Asia WGS AF: 0.603 AC: 2098 AN: 3478

EpiCase AF: 0.751

EpiControl AF: 0.748

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=70/30	polymorphism (auto)

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; COSMIC: COSV60966899; COSMIC: COSV60966899;