rs17100475

Positions:

• chr1-77373795-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174858.3(AK5):​c.891+33227T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 151,978 control chromosomes in the GnomAD database, including 4,810 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 0.24 (4810 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK5	NM_174858.3	c.891+33227T>G		intron_variant		ENST00000354567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK5	ENST00000354567.7	c.891+33227T>G		intron_variant		1	NM_174858.3	P1
AK5	ENST00000344720.9	c.813+33227T>G		intron_variant		1
AK5	ENST00000465146.5	n.164+33227T>G		intron_variant, non_coding_transcript_variant		3
AK5	ENST00000530826.1	n.90+2328T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36930 AN: 151858 Hom.: 4796 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.260

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.243 AC: 36960 AN: 151978 Hom.: 4810 Cov.: 32 AF XY: 0.243 AC XY: 18060 AN XY: 74292

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.256

Alfa AF: 0.235 Hom.: 7350

Bravo AF: 0.257

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.5
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs17100475; hg19: chr1-77839480;