rs148764112

Variant names:

• chr9-132725738-C-A
• rs148764112
• NM_152572.3:c.1390G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-132725738-C-A
• chr9-132725738-C-G
• chr9-132725738-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152572.3(AK8):​c.1390G>T​(p.Glu464*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000139 in 1,438,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AK8 NM_152572.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.65
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK8	NM_152572.3	c.1390G>T	p.Glu464*	stop_gained	Exon 13 of 13	ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.1390G>T	p.Glu464*	stop_gained	Exon 13 of 13	1	NM_152572.3	ENSP00000298545.3
AK8	ENST00000467161.1	n.333G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
AK8	ENST00000476719.1	n.1827G>T		non_coding_transcript_exon_variant	Exon 12 of 12	5
AK8	ENST00000477396.5	n.2305G>T		non_coding_transcript_exon_variant	Exon 15 of 15	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000930 AC: 2 AN: 215144 AF XY: 0.0000174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000685

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438190 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2 AN XY: 712694

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.0000500 AC: 2 AN: 39998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25588

East Asian (EAS) AF: 0.00 AC: 0 AN: 39100

South Asian (SAS) AF: 0.00 AC: 0 AN: 82342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100370

Other (OTH) AF: 0.00 AC: 0 AN: 59668

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000341 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	41
DANN	Uncertain	0.99
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.90	D
PhyloP100		5.6
Vest4		0.24
GERP RS		4.2
Mutation Taster		=90/110	disease causing

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: rs148764112; hg19: chr9-135601125;