rs2072058

Variant names:

• chr9-132874686-G-A
• rs2072058
• NM_152572.3:c.169+429C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AK8	NM_152572.3	c.169+429C>T		intron_variant	Intron 2 of 12	ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.169+429C>T		intron_variant	Intron 2 of 12	1	NM_152572.3	ENSP00000298545.3
AK8	ENST00000476719.1	n.606+3486C>T		intron_variant	Intron 1 of 11	5
AK8	ENST00000477396.5	n.692-247C>T		intron_variant	Intron 2 of 14	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

African (AFR) AF: 0.0996 AC: 4138 AN: 41532

American (AMR) AF: 0.405 AC: 6193 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1866 AN: 3468

East Asian (EAS) AF: 0.358 AC: 1848 AN: 5162

South Asian (SAS) AF: 0.569 AC: 2745 AN: 4822

European-Finnish (FIN) AF: 0.483 AC: 5103 AN: 10576

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31289 AN: 67960

Other (OTH) AF: 0.375 AC: 791 AN: 2110

Alfa AF: 0.385 Hom.: 2645

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
PhyloP100		-0.32
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: rs2072058; hg19: chr9-135750073;