rs387906583
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_000476.3(AK1):c.139delG(p.Val47SerfsTer45) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
AK1
NM_000476.3 frameshift
NM_000476.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.51
Publications
2 publications found
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]
AK1 Gene-Disease associations (from GenCC):
- hemolytic anemia due to adenylate kinase deficiencyInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 9-127872757-AC-A is Pathogenic according to our data. Variant chr9-127872757-AC-A is described in ClinVar as Pathogenic. ClinVar VariationId is 18269.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000476.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AK1 | NM_000476.3 | MANE Select | c.139delG | p.Val47SerfsTer45 | frameshift | Exon 4 of 7 | NP_000467.1 | P00568 | |
| AK1 | NM_001318122.2 | c.187delG | p.Val63SerfsTer45 | frameshift | Exon 3 of 6 | NP_001305051.1 | Q5T9B7 | ||
| AK1 | NM_001318121.1 | c.139delG | p.Val47SerfsTer45 | frameshift | Exon 4 of 7 | NP_001305050.1 | Q6FGX9 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| AK1 | ENST00000644144.2 | MANE Select | c.139delG | p.Val47SerfsTer45 | frameshift | Exon 4 of 7 | ENSP00000494600.1 | P00568 | |
| ENSG00000257524 | ENST00000646171.1 | n.*172delG | non_coding_transcript_exon | Exon 10 of 13 | ENSP00000495484.1 | A0A2R8YFX0 | |||
| ENSG00000257524 | ENST00000646171.1 | n.*172delG | 3_prime_UTR | Exon 10 of 13 | ENSP00000495484.1 | A0A2R8YFX0 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461850Hom.: 0 Cov.: 62 AF XY: 0.00 AC XY: 0AN XY: 727220 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461850
Hom.:
Cov.:
62
AF XY:
AC XY:
0
AN XY:
727220
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53380
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112008
Other (OTH)
AF:
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Hemolytic anemia due to adenylate kinase deficiency (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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