rs7536307

Variant names:

• chr1-77492363-C-T
• rs7536307
• NM_174858.3:c.1147+6011C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174858.3(AK5):​c.1147+6011C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,052 control chromosomes in the GnomAD database, including 27,994 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 0.59 (27994 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.1147+6011C>T		intron_variant	Intron 10 of 13	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.1147+6011C>T		intron_variant	Intron 10 of 13	1	NM_174858.3	ENSP00000346577.2
AK5	ENST00000344720.9	c.1069+6011C>T		intron_variant	Intron 10 of 13	1		ENSP00000341430.5
AK5	ENST00000527263.1	n.109+6011C>T		intron_variant	Intron 3 of 5	3		ENSP00000436859.1
AK5	ENST00000530826.1	n.346+6011C>T		intron_variant	Intron 5 of 7	3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90123 AN: 151934 Hom.: 27973 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.682

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.593 AC: 90192 AN: 152052 Hom.: 27994 Cov.: 32 AF XY: 0.594 AC XY: 44171 AN XY: 74312

African (AFR) AF: 0.403 AC: 16696 AN: 41454

American (AMR) AF: 0.565 AC: 8630 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2537 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3432 AN: 5164

South Asian (SAS) AF: 0.531 AC: 2556 AN: 4818

European-Finnish (FIN) AF: 0.745 AC: 7884 AN: 10580

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.682 AC: 46352 AN: 67968

Other (OTH) AF: 0.612 AC: 1290 AN: 2108

Alfa AF: 0.653 Hom.: 19326

Bravo AF: 0.579

Asia WGS AF: 0.583 AC: 2027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.88
DANN	Benign	0.63
PhyloP100		-0.78
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: rs7536307; hg19: chr1-77958048;