rs121964907
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000027.4(AGA):c.179G>A(p.Gly60Asp) variant causes a missense 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. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G60S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000027.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGA | NM_000027.4 | c.179G>A | p.Gly60Asp | missense_variant | 2/9 | ENST00000264595.7 | |
AGA | NM_001171988.2 | c.179G>A | p.Gly60Asp | missense_variant | 2/9 | ||
AGA | XM_047449722.1 | c.179G>A | p.Gly60Asp | missense_variant | 2/7 | ||
AGA | NR_033655.2 | n.241G>A | non_coding_transcript_exon_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGA | ENST00000264595.7 | c.179G>A | p.Gly60Asp | missense_variant | 2/9 | 1 | NM_000027.4 | P1 | |
AGA | ENST00000506853.5 | n.213G>A | non_coding_transcript_exon_variant | 2/6 | 2 | ||||
AGA | ENST00000510955.5 | n.213G>A | non_coding_transcript_exon_variant | 2/4 | 2 | ||||
AGA | ENST00000511231.1 | n.213G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461850Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727230
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Aspartylglucosaminuria Pathogenic:3Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 09, 2021 | ClinVar contains an entry for this variant (Variation ID: 222). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this variant affects AGA protein function (PMID: 11309371). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces glycine with aspartic acid at codon 60 of the AGA protein (p.Gly60Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with aspartylglucosaminuria (PMID: 1722323). - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 15, 2022 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 15, 1991 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 15, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at