9-132852022-A-G

Variant names:

• chr9-132852022-A-G
• rs2254289
• NM_152572.3:c.402+2835T>C

Variant summary

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

The NM_152572.3(AK8):​c.402+2835T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,066 control chromosomes in the GnomAD database, including 43,171 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 0.75 (43171 hom., cov: 32)
• Consequence: AK8 NM_152572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 10 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 = 0.842 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152572.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK8	NM_152572.3	MANE Select	c.402+2835T>C		intron	N/A	NP_689785.1
	AK8	NM_001371771.1		c.315+2835T>C		intron	N/A	NP_001358700.1
	AK8	NM_001371772.1		c.267+2835T>C		intron	N/A	NP_001358701.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK8	ENST00000298545.4	TSL:1 MANE Select	c.402+2835T>C		intron	N/A	ENSP00000298545.3
	AK8	ENST00000476719.1	TSL:5	n.839+2835T>C		intron	N/A
	AK8	ENST00000477396.5	TSL:2	n.1024+2835T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114086 AN: 151948 Hom.: 43138 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.863

Gnomad FIN AF: 0.830

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.751 AC: 114174 AN: 152066 Hom.: 43171 Cov.: 32 AF XY: 0.754 AC XY: 56092 AN XY: 74348

African (AFR) AF: 0.663 AC: 27487 AN: 41448

American (AMR) AF: 0.727 AC: 11110 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2778 AN: 3470

East Asian (EAS) AF: 0.855 AC: 4423 AN: 5176

South Asian (SAS) AF: 0.864 AC: 4172 AN: 4828

European-Finnish (FIN) AF: 0.830 AC: 8777 AN: 10572

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53037 AN: 67988

Other (OTH) AF: 0.736 AC: 1549 AN: 2106

Alfa AF: 0.774 Hom.: 25166

Bravo AF: 0.736

Asia WGS AF: 0.854 AC: 2969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.39
PhyloP100		-2.9
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: rs2254289; hg19: chr9-135727409;