rs281865019
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_024312.5(GNPTAB):c.3458A>G(p.Asn1153Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. N1153N) has been classified as Likely benign.
Frequency
Consequence
NM_024312.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GNPTAB | ENST00000299314.12 | c.3458A>G | p.Asn1153Ser | missense_variant | Exon 19 of 21 | 1 | NM_024312.5 | ENSP00000299314.7 | ||
GNPTAB | ENST00000549738.5 | n.*65A>G | non_coding_transcript_exon_variant | Exon 4 of 5 | 4 | ENSP00000450161.1 | ||||
GNPTAB | ENST00000549738.5 | n.*65A>G | 3_prime_UTR_variant | Exon 4 of 5 | 4 | ENSP00000450161.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461712Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727180 show subpopulations
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Mucolipidosis Pathogenic:1
Variant summary: GNPTAB c.3458A>G (p.Asn1153Ser) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant was absent in 251162 control chromosomes. c.3458A>G has been observed in a compound heterozygous individual affected with Mucolipidosis (Otomo_2009). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in about 2% of normal activity in an in vitro assay (Qian_2015). The following publications have been ascertained in the context of this evaluation (PMID: 19197337, 25505245). ClinVar contains an entry for this variant (Variation ID: 39075). Based on the evidence outlined above, the variant was classified as likely pathogenic. -
Pseudo-Hurler polydystrophy Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at