rs2072058

Positions:

• chr9-132874686-G-A

Variant summary

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

The NM_152572.3(AK8):​c.169+429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,114 control chromosomes in the GnomAD database, including 11,829 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 0.36 (11829 hom., cov: 32)
• Consequence: AK8 NM_152572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK8	NM_152572.3	c.169+429C>T		intron_variant		ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.169+429C>T		intron_variant		1	NM_152572.3	ENSP00000298545	P1
AK8	ENST00000476719.1	n.606+3486C>T		intron_variant, non_coding_transcript_variant		5
AK8	ENST00000477396.5	n.692-247C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54493 AN: 151996 Hom.: 11823 Cov.: 32

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.358 AC: 54493 AN: 152114 Hom.: 11829 Cov.: 32 AF XY: 0.365 AC XY: 27139 AN XY: 74376

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.375

Alfa AF: 0.392 Hom.: 2642

Bravo AF: 0.335

Asia WGS AF: 0.456 AC: 1583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.63

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: rs2072058; hg19: chr9-135750073;