rs1167206

Positions:

• chr1-77297857-A-C
• chr1-77297857-A-G
• chr1-77297857-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_174858.3(AK5):​c.609A>C​(p.Lys203Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: AK5 NM_174858.3 missense
• 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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.775

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK5	NM_174858.3	c.609A>C	p.Lys203Asn	missense_variant	5/14	ENST00000354567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK5	ENST00000354567.7	c.609A>C	p.Lys203Asn	missense_variant	5/14	1	NM_174858.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DEOGEN2	Uncertain	0.56	D;.
LIST_S2	Uncertain	0.93	D;D
MetaRNN	Pathogenic	0.78	D;D
PROVEAN	Uncertain	-3.1	D;D
Sift	Benign	0.10	T;D
Sift4G	Uncertain	0.0020	D;D
Vest4		0.72
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1167206; hg19: chr1-77763542;