Menu
GeneBe

1-77297661-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174858.3(AK5):c.518G>A(p.Ser173Asn) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AK5
NM_174858.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56
Variant links:
Genes affected
AK5 (HGNC:365): (adenylate kinase 5) This gene encodes a member of the adenylate kinase family, which is involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. This member is related to the UMP/CMP kinase of several species. It is located in the cytosol and expressed exclusively in brain. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1850287).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AK5NM_174858.3 linkuse as main transcriptc.518G>A p.Ser173Asn missense_variant 4/14 ENST00000354567.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AK5ENST00000354567.7 linkuse as main transcriptc.518G>A p.Ser173Asn missense_variant 4/141 NM_174858.3 P1Q9Y6K8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsFeb 11, 2022The c.518G>A (p.S173N) alteration is located in exon 4 (coding exon 4) of the AK5 gene. This alteration results from a G to A substitution at nucleotide position 518, causing the serine (S) at amino acid position 173 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
Cadd
Benign
15
Dann
Uncertain
0.98
DEOGEN2
Benign
0.17
T;.;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.74
D
LIST_S2
Benign
0.79
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.015
N;.;.
MutationTaster
Benign
0.87
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
0.060
N;N;N
REVEL
Benign
0.20
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.52
T;T;T
Polyphen
0.0010
B;.;.
Vest4
0.14
MutPred
0.48
Loss of phosphorylation at S173 (P = 0.0495);.;.;
MVP
0.68
MPC
0.45
ClinPred
0.40
T
GERP RS
2.0
Varity_R
0.076
gMVP
0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-77763346; API