rs778703128
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_153676.4(USH1C):c.1556C>T(p.Pro519Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000939 in 1,596,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P519S) has been classified as Likely benign.
Frequency
Consequence
NM_153676.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1C | NM_153676.4 | c.1556C>T | p.Pro519Leu | missense_variant | 18/27 | ENST00000005226.12 | |
USH1C | NM_005709.4 | c.1284+7588C>T | intron_variant | ENST00000318024.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1C | ENST00000005226.12 | c.1556C>T | p.Pro519Leu | missense_variant | 18/27 | 5 | NM_153676.4 | ||
USH1C | ENST00000318024.9 | c.1284+7588C>T | intron_variant | 1 | NM_005709.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000427 AC: 1AN: 234366Hom.: 0 AF XY: 0.00000778 AC XY: 1AN XY: 128556
GnomAD4 exome AF: 0.00000969 AC: 14AN: 1444886Hom.: 0 Cov.: 38 AF XY: 0.0000139 AC XY: 10AN XY: 718818
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152092Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
Usher syndrome type 1C;C1865870:Autosomal recessive nonsyndromic hearing loss 18A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 01, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 12, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at