9-132833994-T-C

Variant names:

• chr9-132833994-T-C
• rs944028
• NM_152572.3:c.403-5268A>G

Variant summary

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

The NM_152572.3(AK8):​c.403-5268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,248 control chromosomes in the GnomAD database, including 3,453 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 0.20 (3453 hom., cov: 33)
• Consequence: AK8 NM_152572.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 2 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK8	NM_152572.3	c.403-5268A>G		intron_variant	Intron 5 of 12	ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.403-5268A>G		intron_variant	Intron 5 of 12	1	NM_152572.3	ENSP00000298545.3
AK8	ENST00000476719.1	n.840-5268A>G		intron_variant	Intron 4 of 11	5
AK8	ENST00000477396.5	n.1025-5268A>G		intron_variant	Intron 6 of 14	2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30974 AN: 152130 Hom.: 3447 Cov.: 33

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.204 AC: 30988 AN: 152248 Hom.: 3453 Cov.: 33 AF XY: 0.205 AC XY: 15275 AN XY: 74430

African (AFR) AF: 0.186 AC: 7720 AN: 41550

American (AMR) AF: 0.142 AC: 2165 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2270 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4820

European-Finnish (FIN) AF: 0.289 AC: 3063 AN: 10604

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13722 AN: 68018

Other (OTH) AF: 0.186 AC: 393 AN: 2112

Alfa AF: 0.220 Hom.: 476

Bravo AF: 0.193

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.75
PhyloP100		-0.093
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: rs944028; hg19: chr9-135709381;