rs544952984
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_173477.5(USH1G):āc.717G>Cā(p.Lys239Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000212 in 1,603,180 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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. K239Q) has been classified as Likely benign.
Frequency
Consequence
NM_173477.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
USH1G | NM_173477.5 | c.717G>C | p.Lys239Asn | missense_variant | 2/3 | ENST00000614341.5 | |
USH1G | NM_001282489.3 | c.408G>C | p.Lys136Asn | missense_variant | 2/3 | ||
USH1G | XM_011524296.2 | c.408G>C | p.Lys136Asn | missense_variant | 2/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
USH1G | ENST00000614341.5 | c.717G>C | p.Lys239Asn | missense_variant | 2/3 | 1 | NM_173477.5 | P1 | |
USH1G | ENST00000579243.1 | c.*316G>C | 3_prime_UTR_variant, NMD_transcript_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000722 AC: 11AN: 152260Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000449 AC: 108AN: 240548Hom.: 2 AF XY: 0.000646 AC XY: 85AN XY: 131562
GnomAD4 exome AF: 0.000227 AC: 329AN: 1450802Hom.: 2 Cov.: 41 AF XY: 0.000346 AC XY: 250AN XY: 722266
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152378Hom.: 0 Cov.: 32 AF XY: 0.0000939 AC XY: 7AN XY: 74524
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2020 | - - |
Usher syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation | Dec 31, 2022 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 19, 2013 | The Lys239Asn variant in USH1G has not been previously reported in individuals w ith hearing loss or in large population studies. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do no t provide strong support for or against an impact to the protein. In summary, ad ditional information is needed to fully assess the clinical significance of this variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at