GeneBe

rs1055574

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153676.4(USH1C):​c.*46T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

USH1C
NM_153676.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0870

Publications

21 publications found
Variant links:
Genes affected
USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]
USH1C Gene-Disease associations (from GenCC):
  • Usher syndrome type 1
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Usher syndrome type 1C
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
  • autosomal recessive nonsyndromic hearing loss 18A
    Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • nonsyndromic genetic hearing loss
    Inheritance: AR Classification: LIMITED Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
USH1CNM_153676.4 linkc.*46T>G 3_prime_UTR_variant Exon 27 of 27 ENST00000005226.12 NP_710142.1 Q9Y6N9-5
USH1CNM_005709.4 linkc.*78T>G 3_prime_UTR_variant Exon 21 of 21 ENST00000318024.9 NP_005700.2 Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
USH1CENST00000005226.12 linkc.*46T>G 3_prime_UTR_variant Exon 27 of 27 5 NM_153676.4 ENSP00000005226.7 Q9Y6N9-5
USH1CENST00000318024.9 linkc.*78T>G 3_prime_UTR_variant Exon 21 of 21 1 NM_005709.4 ENSP00000317018.4 Q9Y6N9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1440538
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
714486
African (AFR)
AF:
0.00
AC:
0
AN:
33060
American (AMR)
AF:
0.00
AC:
0
AN:
42058
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25764
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39072
South Asian (SAS)
AF:
0.00
AC:
0
AN:
82852
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52174
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5596
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1100318
Other (OTH)
AF:
0.00
AC:
0
AN:
59644
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
50437

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.8
DANN
Benign
0.61
PhyloP100
-0.087

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1055574; hg19: chr11-17515833; API