chr17-74922989-C-CG
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_173477.5(USH1G):c.84_85insC(p.Asp29ArgfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000425 in 1,412,594 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P28P) has been classified as Likely benign.
Frequency
Consequence
NM_173477.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.84_85insC | p.Asp29ArgfsTer29 | frameshift_variant | 1/3 | ENST00000614341.5 | |
USH1G | NM_001282489.3 | c.-173_-172insC | 5_prime_UTR_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.84_85insC | p.Asp29ArgfsTer29 | frameshift_variant | 1/3 | 1 | NM_173477.5 | P1 | |
OTOP2 | ENST00000580223.2 | c.-271dup | 5_prime_UTR_variant | 1/5 | 1 | ||||
USH1G | ENST00000579243.1 | c.84_85insC | p.Asp29ArgfsTer49 | frameshift_variant, NMD_transcript_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000425 AC: 6AN: 1412594Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1AN XY: 697522
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74330
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | USH1G: PVS1, PM2, PM3 - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | This sequence change creates a premature translational stop signal (p.Asp29Argfs*29) in the USH1G gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in USH1G are known to be pathogenic (PMID: 12588794, 22219650). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Usher syndrome type 1 (PMID: 21569298, 32531858). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at