14-20693674-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PP3_Strong
The NM_001097577.3(ANG):c.110A>G(p.His37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,082 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H37H) has been classified as Likely benign.
Frequency
Consequence
NM_001097577.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANG | NM_001097577.3 | c.110A>G | p.His37Arg | missense_variant | 2/2 | ENST00000397990.5 | |
RNASE4 | NM_002937.5 | c.-17-5681A>G | intron_variant | ENST00000555835.3 | |||
EGILA | NR_174964.1 | n.542T>C | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANG | ENST00000397990.5 | c.110A>G | p.His37Arg | missense_variant | 2/2 | 1 | NM_001097577.3 | P1 | |
RNASE4 | ENST00000555835.3 | c.-17-5681A>G | intron_variant | 1 | NM_002937.5 | P1 | |||
EGILA | ENST00000554286.1 | n.721T>C | non_coding_transcript_exon_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251494Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135922
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727248
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2022 | 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1381736). This missense change has been observed in individual(s) with Parkinson disease (PMID: 22190368). This variant is present in population databases (rs756137289, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 37 of the ANG protein (p.His37Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at