4-127669126-G-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015693.4(INTU):c.1063G>T(p.Glu355*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_015693.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INTU | ENST00000335251.11 | c.1063G>T | p.Glu355* | stop_gained | Exon 5 of 16 | 1 | NM_015693.4 | ENSP00000334003.5 | ||
INTU | ENST00000503952.5 | n.1063G>T | non_coding_transcript_exon_variant | Exon 5 of 17 | 1 | ENSP00000421995.1 | ||||
INTU | ENST00000503626.5 | n.1063G>T | non_coding_transcript_exon_variant | Exon 5 of 18 | 2 | ENSP00000426287.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 23
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Short-rib thoracic dysplasia 20 with polydactyly Pathogenic:2
This variant is interpreted as Likely Pathogenic, for Short-rib thoracic dysplasia 20 with polydactyly, autosomal recessive. The following ACMG Tag(s) were applied: PS3 => Well-established functional studies show a deleterious effect (https://www.ncbi.nlm.nih.gov/pubmed/27158779). PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PVS1-Moderate => PVS1 downgraded in strength to Moderate. PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
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Short rib-polydactyly syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at