rs137853205
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000476.3(AK1):c.190G>A(p.Gly64Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,000 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 Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
AK1
NM_000476.3 missense
NM_000476.3 missense
Scores
16
1
1
Clinical Significance
Conservation
PhyloP100: 7.51
Genes affected
AK1 (HGNC:361): (adenylate kinase 1) This gene encodes an adenylate kinase enzyme involved in energy metabolism and homeostasis of cellular adenine nucleotide ratios in different intracellular compartments. This gene is highly expressed in skeletal muscle, brain and erythrocytes. Certain mutations in this gene resulting in a functionally inadequate enzyme are associated with a rare genetic disorder causing nonspherocytic hemolytic anemia. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. This gene shares readthrough transcripts with the upstream ST6GALNAC6 gene. [provided by RefSeq, Jan 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PM1
?
In a chain Adenylate kinase isoenzyme 1 (size 193) in uniprot entity KAD1_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_000476.3
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.992
PP5
?
Variant 9-127872707-C-T is Pathogenic according to our data. Variant chr9-127872707-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 18267.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AK1 | NM_000476.3 | c.190G>A | p.Gly64Arg | missense_variant | 4/7 | ENST00000644144.2 | |
ST6GALNAC4-ST6GALNAC6-AK1 | NR_174625.1 | n.3509G>A | non_coding_transcript_exon_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AK1 | ENST00000644144.2 | c.190G>A | p.Gly64Arg | missense_variant | 4/7 | NM_000476.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
2
AN:
152164
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251326Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135858
GnomAD3 exomes
AF:
AC:
1
AN:
251326
Hom.:
AF XY:
AC XY:
1
AN XY:
135858
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461836Hom.: 0 Cov.: 63 AF XY: 0.00000138 AC XY: 1AN XY: 727212
GnomAD4 exome
AF:
AC:
4
AN:
1461836
Hom.:
Cov.:
63
AF XY:
AC XY:
1
AN XY:
727212
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
GnomAD4 genome
?
AF:
AC:
2
AN:
152164
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74348
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hemolytic anemia due to adenylate kinase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;D;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H;.
MutationTaster
Benign
A;A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D
Sift4G
Pathogenic
D;.;D;D
Polyphen
D;D;D;.
Vest4
MutPred
Loss of ubiquitination at K63 (P = 0.0353);Loss of ubiquitination at K63 (P = 0.0353);Loss of ubiquitination at K63 (P = 0.0353);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at