9-132792695-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_152572.3(AK8):c.1060G>A(p.Gly354Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000206 in 1,556,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )
Consequence
AK8
NM_152572.3 missense
NM_152572.3 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 3.60
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.935
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AK8 | NM_152572.3 | c.1060G>A | p.Gly354Ser | missense_variant | 11/13 | ENST00000298545.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AK8 | ENST00000298545.4 | c.1060G>A | p.Gly354Ser | missense_variant | 11/13 | 1 | NM_152572.3 | P1 | |
AK8 | ENST00000476719.1 | n.1497G>A | non_coding_transcript_exon_variant | 10/12 | 5 | ||||
AK8 | ENST00000477396.5 | n.1975G>A | non_coding_transcript_exon_variant | 13/15 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000364 AC: 6AN: 164804Hom.: 0 AF XY: 0.0000230 AC XY: 2AN XY: 86940
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GnomAD4 exome AF: 0.0000178 AC: 25AN: 1404140Hom.: 0 Cov.: 30 AF XY: 0.0000188 AC XY: 13AN XY: 693118
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 23, 2021 | The c.1060G>A (p.G354S) alteration is located in exon 11 (coding exon 11) of the AK8 gene. This alteration results from a G to A substitution at nucleotide position 1060, causing the glycine (G) at amino acid position 354 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.1398);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at