chr1-114684369-CAA-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000036.3(AMPD1):​c.382-7_382-6delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,124,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AMPD1
NM_000036.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

0 publications found
Variant links:
Genes affected
AMPD1 (HGNC:468): (adenosine monophosphate deaminase 1) Adenosine monophosphate deaminase 1 catalyzes the deamination of AMP to IMP in skeletal muscle and plays an important role in the purine nucleotide cycle. Two other genes have been identified, AMPD2 and AMPD3, for the liver- and erythocyte-specific isoforms, respectively. Deficiency of the muscle-specific enzyme is apparently a common cause of exercise-induced myopathy and probably the most common cause of metabolic myopathy in the human. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]
AMPD1 Gene-Disease associations (from GenCC):
  • myopathy due to myoadenylate deaminase deficiency
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • adenosine monophosphate deaminase deficiency
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AMPD1NM_000036.3 linkc.382-7_382-6delTT splice_region_variant, intron_variant Intron 4 of 15 ENST00000520113.7 NP_000027.3 P23109-1
AMPD1NM_001172626.2 linkc.370-7_370-6delTT splice_region_variant, intron_variant Intron 3 of 14 NP_001166097.2 P23109-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AMPD1ENST00000520113.7 linkc.382-7_382-6delTT splice_region_variant, intron_variant Intron 4 of 15 1 NM_000036.3 ENSP00000430075.3 P23109-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
134456
Hom.:
0
Cov.:
32
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000255
AC:
18
AN:
70624
AF XY:
0.000188
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000429
Gnomad FIN exome
AF:
0.000878
Gnomad NFE exome
AF:
0.000297
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
13
AN:
1124668
Hom.:
0
AF XY:
0.0000142
AC XY:
8
AN XY:
562978
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000388
AC:
1
AN:
25782
American (AMR)
AF:
0.00
AC:
0
AN:
36144
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20774
East Asian (EAS)
AF:
0.00
AC:
0
AN:
31064
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71712
European-Finnish (FIN)
AF:
0.000171
AC:
7
AN:
40820
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4762
European-Non Finnish (NFE)
AF:
0.00000472
AC:
4
AN:
846930
Other (OTH)
AF:
0.0000214
AC:
1
AN:
46680
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
134456
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
64854
African (AFR)
AF:
0.00
AC:
0
AN:
36552
American (AMR)
AF:
0.00
AC:
0
AN:
13272
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3220
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4738
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4210
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
7764
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
296
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
61778
Other (OTH)
AF:
0.00
AC:
0
AN:
1808

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.0
Mutation Taster
=95/5
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs727503806; hg19: chr1-115226990; COSMIC: COSV62415940; API