12-101757217-G-GT
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024312.5(GNPTAB):c.3428_3429insA(p.Asn1143LysfsTer3) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000043 in 1,396,862 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. N1143N) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_024312.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GNPTAB | NM_024312.5 | c.3428_3429insA | p.Asn1143LysfsTer3 | frameshift_variant | 18/21 | ENST00000299314.12 | |
GNPTAB | XM_006719593.4 | c.3428_3429insA | p.Asn1143LysfsTer3 | frameshift_variant | 18/19 | ||
GNPTAB | XM_011538731.3 | c.3347_3348insA | p.Asn1116LysfsTer3 | frameshift_variant | 18/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.3428_3429insA | p.Asn1143LysfsTer3 | frameshift_variant | 18/21 | 1 | NM_024312.5 | P1 | |
GNPTAB | ENST00000550718.1 | c.240_241insA | p.Asn81LysfsTer3 | frameshift_variant | 3/4 | 3 | |||
GNPTAB | ENST00000549194.1 | n.294_295insA | non_coding_transcript_exon_variant | 3/3 | 3 | ||||
GNPTAB | ENST00000549738.5 | c.179_180insA | p.Asn60LysfsTer3 | frameshift_variant, NMD_transcript_variant | 2/5 | 4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000430 AC: 6AN: 1396862Hom.: 0 Cov.: 25 AF XY: 0.00000429 AC XY: 3AN XY: 698644
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Pseudo-Hurler polydystrophy;C2673377:Mucolipidosis type II Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2021 | This sequence change creates a premature translational stop signal (p.Asn1143Lysfs*3) in the GNPTAB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GNPTAB are known to be pathogenic (PMID: 19617216, 25107912). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mucolipidosis II (PMID: 19197337). This variant is also known as c.3428_3429insA. ClinVar contains an entry for this variant (Variation ID: 39072). For these reasons, this variant has been classified as Pathogenic. - |
Mucolipidosis type II Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at