rs61752479
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000036.3(AMPD1):c.143C>T(p.Pro48Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,946 control chromosomes in the GnomAD database, including 11,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity,other (no stars). Synonymous variant affecting the same amino acid position (i.e. P48P) has been classified as Likely benign.
Frequency
Consequence
NM_000036.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AMPD1 | ENST00000520113.7 | c.143C>T | p.Pro48Leu | missense_variant | Exon 3 of 16 | 1 | NM_000036.3 | ENSP00000430075.3 | ||
AMPD1 | ENST00000369538.4 | c.131C>T | p.Pro44Leu | missense_variant | Exon 2 of 15 | 2 | ENSP00000358551.4 | |||
AMPD1 | ENST00000637080.1 | n.146C>T | non_coding_transcript_exon_variant | Exon 2 of 14 | 5 | ENSP00000489753.1 |
Frequencies
GnomAD3 genomes AF: 0.0865 AC: 13148AN: 152026Hom.: 781 Cov.: 32
GnomAD3 exomes AF: 0.0876 AC: 22018AN: 251420Hom.: 1331 AF XY: 0.0888 AC XY: 12065AN XY: 135876
GnomAD4 exome AF: 0.115 AC: 167963AN: 1461802Hom.: 10780 Cov.: 32 AF XY: 0.113 AC XY: 82083AN XY: 727200
GnomAD4 genome AF: 0.0864 AC: 13146AN: 152144Hom.: 781 Cov.: 32 AF XY: 0.0837 AC XY: 6223AN XY: 74378
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2Other:1
- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).
This variant is associated with the following publications: (PMID: 1631143, 33250842, 21228398, 20981092) -
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Muscle AMP deaminase deficiency Uncertain:1Benign:2
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The p.Pro81Leu variant in the AMPD1 gene has been previously reported in 11 unrelated individuals with reported AMPD deficiency (Morisaki et al., 1992). Of note, all individuals were homozygous for this variant as well as the p.Gln45* variant. The highest allele frequency of the p.Pro81Leu variant was identified in the European population at 17,214/129,128 chromosomes (13.33%) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational tools predict that the p.Pro81Leu variant is deleterious; however, the accuracy of in silico algorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Pro81Leu variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: PP3] -
AMPD1-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at