9-91214365-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001698.3(AUH):c.1003C>T(p.Arg335Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,609,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R335H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001698.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AUH | NM_001698.3 | c.1003C>T | p.Arg335Cys | missense_variant | 10/10 | ENST00000375731.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AUH | ENST00000375731.9 | c.1003C>T | p.Arg335Cys | missense_variant | 10/10 | 1 | NM_001698.3 | P1 | |
AUH | ENST00000303617.5 | c.916C>T | p.Arg306Cys | missense_variant | 9/9 | 1 | |||
AUH | ENST00000473695.1 | n.227C>T | non_coding_transcript_exon_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000814 AC: 2AN: 245596Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132894
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1457508Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 724970
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74318
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2021 | The c.1003C>T (p.R335C) alteration is located in exon 10 (coding exon 10) of the AUH gene. This alteration results from a C to T substitution at nucleotide position 1003, causing the arginine (R) at amino acid position 335 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
3-methylglutaconic aciduria type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 02, 2021 | This variant has not been reported in the literature in individuals with AUH-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is present in population databases (rs772918339, ExAC 0.002%). This sequence change replaces arginine with cysteine at codon 335 of the AUH protein (p.Arg335Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at