rs1555486629
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014714.4(IFT140):c.2278C>T(p.Arg760Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,738 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_014714.4 stop_gained
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 |
---|---|---|---|---|---|---|---|
IFT140 | NM_014714.4 | c.2278C>T | p.Arg760Ter | stop_gained | 19/31 | ENST00000426508.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT140 | ENST00000426508.7 | c.2278C>T | p.Arg760Ter | stop_gained | 19/31 | 5 | NM_014714.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461738Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727172
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Saldino-Mainzer syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 13, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 446316). This premature translational stop signal has been observed in individual(s) with clinical features of short-rib thoracic dysplasia (PMID: 28288023). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg760*) in the IFT140 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT140 are known to be pathogenic (PMID: 22503633, 23418020, 24009529, 26216056). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at