9-132814658-A-G

Variant names:

• chr9-132814658-A-G
• rs1030833830
• NM_152572.3:c.959T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152572.3(AK8):​c.959T>C​(p.Phe320Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. F320C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AK8 NM_152572.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK8	NM_152572.3	c.959T>C	p.Phe320Ser	missense_variant	Exon 10 of 13	ENST00000298545.4	NP_689785.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK8	ENST00000298545.4	c.959T>C	p.Phe320Ser	missense_variant	Exon 10 of 13	1	NM_152572.3	ENSP00000298545.3
AK8	ENST00000476719.1	n.1396T>C		non_coding_transcript_exon_variant	Exon 9 of 12	5
AK8	ENST00000477396.5	n.1874T>C		non_coding_transcript_exon_variant	Exon 12 of 15	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.52	T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.0
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.36
Sift	Benign	0.17	T
Sift4G	Benign	0.076	T
Polyphen		0.12	B
Vest4		0.54
MutPred		0.65		Gain of disorder (P = 0.0043);
MVP		0.53
MPC		0.46
ClinPred		0.88	D
GERP RS		0.029
Varity_R		0.16
gMVP		0.74
Mutation Taster		=94/6	polymorphism

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: rs1030833830; hg19: chr9-135690045;