rs1179521659

Variant names:

• chr9-132823301-C-A
• rs1179521659
• NM_152572.3:c.793G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-132823301-C-A
• chr9-132823301-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.793G>T​(p.Ala265Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A265T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AK8 NM_152572.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61
• Publications: 0 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.793G>T	p.Ala265Ser	missense_variant	Exon 9 of 13	ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.793G>T	p.Ala265Ser	missense_variant	Exon 9 of 13	1	NM_152572.3	ENSP00000298545.3
AK8	ENST00000476719.1	n.1230G>T		non_coding_transcript_exon_variant	Exon 8 of 12	5
AK8	ENST00000477396.5	n.1708G>T		non_coding_transcript_exon_variant	Exon 11 of 15	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461544 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727072

African (AFR) AF: 0.0000598 AC: 2 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111812

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	2.0	M
PhyloP100		5.6
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Benign	0.17	T
Polyphen		0.76	P
Vest4		0.62
MutPred		0.46		Gain of disorder (P = 0.0184);
MVP		0.79
MPC		0.49
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.21
gMVP		0.25
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1179521659; hg19: chr9-135698688;