rs12552369

Positions:

• chr9-132757106-G-A
• chr9-132757106-G-C

Variant summary

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

The NM_152572.3(AK8):​c.1122-29572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,040 control chromosomes in the GnomAD database, including 13,806 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 0.38 (13806 hom., cov: 33)
• Consequence: AK8 NM_152572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630

Genes affected

AK8 (HGNC:26526): (adenylate kinase 8) Enables AMP binding activity and nucleobase-containing compound kinase activity. Involved in nucleoside diphosphate phosphorylation and nucleoside triphosphate biosynthetic process. Located in 9+2 motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK8	NM_152572.3	c.1122-29572C>T		intron_variant		ENST00000298545.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK8	ENST00000298545.4	c.1122-29572C>T		intron_variant		1	NM_152572.3	P1
AK8	ENST00000476719.1	n.1559-29572C>T		intron_variant, non_coding_transcript_variant		5
AK8	ENST00000477396.5	n.2037-29572C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58306 AN: 151922 Hom.: 13788 Cov.: 33

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.705

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.384 AC: 58332 AN: 152040 Hom.: 13806 Cov.: 33 AF XY: 0.391 AC XY: 29039 AN XY: 74312

Gnomad4 AFR AF: 0.0958

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.402

Alfa AF: 0.463 Hom.: 14351

Bravo AF: 0.364

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.98
DANN	Benign	0.88

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: rs12552369; hg19: chr9-135632493;