3-121993167-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001199799.2(ILDR1):āc.1582A>Gā(p.Ser528Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001199799.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ILDR1 | NM_001199799.2 | c.1582A>G | p.Ser528Gly | missense_variant | 7/8 | ENST00000344209.10 | NP_001186728.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ILDR1 | ENST00000344209.10 | c.1582A>G | p.Ser528Gly | missense_variant | 7/8 | 1 | NM_001199799.2 | ENSP00000345667 | P2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1452960Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1AN XY: 721844
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 28, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Ser528Gly var iant in ILDR1 has not been previously reported in individuals with hearing loss. Data from large population studies are insufficient to assess the frequency of this variant. Serine (Ser) at position 528 is not conserved in mammals or evolut ionarily distant species and 2 avian species (chicken and turkey) carry a glycin e (Gly) at the position, raising the possibility that this change may be tolerat ed. Additional computational prediction tools suggest that the variant may not i mpact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Ser528Gly va riant is uncertain, the lack of conservation suggests that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at