8-43140525-C-CGCTGCTGCTGGCCGCGTCCGT
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_152419.3(HGSNAT):c.34_54dup(p.Leu12_Leu18dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,103,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A10A) has been classified as Uncertain significance.
Frequency
Consequence
NM_152419.3 inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HGSNAT | NM_152419.3 | c.34_54dup | p.Leu12_Leu18dup | inframe_insertion | 1/18 | ENST00000379644.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HGSNAT | ENST00000379644.9 | c.34_54dup | p.Leu12_Leu18dup | inframe_insertion | 1/18 | 2 | NM_152419.3 | P3 | |
HGSNAT | ENST00000520704.1 | c.-117_-97dup | 5_prime_UTR_variant, NMD_transcript_variant | 1/10 | 1 | ||||
HGSNAT | ENST00000517319.1 | c.34_54dup | p.Leu12_Leu18dup | inframe_insertion, NMD_transcript_variant | 1/5 | 4 |
Frequencies
GnomAD3 genomes AF: 0.000108 AC: 16AN: 148468Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.000142 AC: 136AN: 955390Hom.: 0 Cov.: 29 AF XY: 0.000149 AC XY: 67AN XY: 450448
GnomAD4 genome AF: 0.000108 AC: 16AN: 148576Hom.: 0 Cov.: 32 AF XY: 0.000124 AC XY: 9AN XY: 72470
ClinVar
Submissions by phenotype
Mucopolysaccharidosis, MPS-III-C Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 05, 2017 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 17, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 14, 2018 | Variant summary: HGSNAT c.34_54dup21 (p.Leu12_Leu18dup) results in an in-frame insertion that is predicted to insert 7 amino acids into the encoded protein. The variant allele was found at a frequency of 7.5e-05 in 26610 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in HGSNAT causing Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) (7.5e-05 vs 0.001), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.34_54dup21 in individuals affected with Mucopolysaccharidosis Type IIIC (Sanfilippo Syndrome C) and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Mucopolysaccharidosis, MPS-III-C;C4225287:Retinitis pigmentosa 73 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This variant, c.34_54dup, results in the insertion of 7 amino acid(s) of the HGSNAT protein (p.Leu12_Leu18dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with HGSNAT-related conditions. ClinVar contains an entry for this variant (Variation ID: 550260). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at