rs944028

Positions:

• chr9-132833994-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.85).
• 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/exons	MANE	UniProt
AK8	NM_152572.3	c.403-5268A>G		intron_variant		ENST00000298545.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK8	ENST00000298545.4	c.403-5268A>G		intron_variant		1	NM_152572.3	P1
AK8	ENST00000476719.1	n.840-5268A>G		intron_variant, non_coding_transcript_variant		5
AK8	ENST00000477396.5	n.1025-5268A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.186

Alfa AF: 0.220 Hom.: 458

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

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: rs944028; hg19: chr9-135709381;