rs17100475

Variant names:

• chr1-77373795-T-G
• rs17100475
• NM_174858.3:c.891+33227T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ENSG00000233099 (HGNC:40069):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.891+33227T>G		intron_variant	Intron 6 of 13	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.891+33227T>G		intron_variant	Intron 6 of 13	1	NM_174858.3	ENSP00000346577.2

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

African (AFR) AF: 0.238 AC: 9870 AN: 41444

American (AMR) AF: 0.334 AC: 5103 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3470

East Asian (EAS) AF: 0.394 AC: 2035 AN: 5160

South Asian (SAS) AF: 0.371 AC: 1788 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1365 AN: 10542

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15136 AN: 67960

Other (OTH) AF: 0.256 AC: 541 AN: 2112

Alfa AF: 0.237 Hom.: 16893

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
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17100475; hg19: chr1-77839480;