rs1003490
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001292063.2(OTOG):āc.5459C>Gā(p.Ala1820Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,549,914 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1820V) has been classified as Benign.
Frequency
Consequence
NM_001292063.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOG | NM_001292063.2 | c.5459C>G | p.Ala1820Gly | missense_variant | 36/56 | ENST00000399397.6 | |
OTOG | NM_001277269.2 | c.5495C>G | p.Ala1832Gly | missense_variant | 35/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOG | ENST00000399397.6 | c.5459C>G | p.Ala1820Gly | missense_variant | 36/56 | 5 | NM_001292063.2 | P2 | |
OTOG | ENST00000399391.7 | c.5495C>G | p.Ala1832Gly | missense_variant | 35/55 | 5 | A2 | ||
OTOG | ENST00000342528.2 | n.2797C>G | non_coding_transcript_exon_variant | 12/22 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00935 AC: 1422AN: 152166Hom.: 20 Cov.: 33
GnomAD3 exomes AF: 0.00192 AC: 285AN: 148604Hom.: 4 AF XY: 0.00141 AC XY: 113AN XY: 79980
GnomAD4 exome AF: 0.000972 AC: 1359AN: 1397630Hom.: 19 Cov.: 69 AF XY: 0.000812 AC XY: 560AN XY: 689360
GnomAD4 genome ? AF: 0.00935 AC: 1424AN: 152284Hom.: 20 Cov.: 33 AF XY: 0.00900 AC XY: 670AN XY: 74458
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 20, 2015 | p.Ala1832Gly in exon 35 of OTOG: This variant is not expected to have clinical s ignificance because it has been identified in 3.6% (34/940) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs1003490). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at