rs1554125752
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003322.6(TULP1):c.855_856insC(p.Val286ArgfsTer98) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,212 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P285P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_003322.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TULP1 | NM_003322.6 | c.855_856insC | p.Val286ArgfsTer98 | frameshift_variant | 10/15 | ENST00000229771.11 | |
LOC124901309 | XR_007059561.1 | n.76-2075dup | intron_variant, non_coding_transcript_variant | ||||
TULP1 | NM_001289395.2 | c.696_697insC | p.Val233ArgfsTer98 | frameshift_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TULP1 | ENST00000229771.11 | c.855_856insC | p.Val286ArgfsTer98 | frameshift_variant | 10/15 | 1 | NM_003322.6 | P4 | |
TULP1 | ENST00000322263.8 | c.696_697insC | p.Val233ArgfsTer98 | frameshift_variant | 9/14 | 1 | A2 | ||
TULP1 | ENST00000614066.4 | c.849_850insC | p.Val284ArgfsTer98 | frameshift_variant | 9/14 | 5 | A2 | ||
TULP1 | ENST00000373892.4 | n.457_458insC | non_coding_transcript_exon_variant | 4/6 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461212Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726918
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2023 | This sequence change creates a premature translational stop signal (p.Val286Argfs*98) in the TULP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TULP1 are known to be pathogenic (PMID: 8606774, 10549638, 15024725, 18055821). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TULP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 505327). For these reasons, this variant has been classified as Pathogenic. - |
Retinitis pigmentosa;C0339527:Leber congenital amaurosis Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 05, 2016 | The p.Val286ArgfsX98 variant in TULP1 has not been reported in patients and it w as absent from large population studies. This variant is predicted to cause a fr ameshift, which alters the protein?s amino acid sequence beginning at position 2 86 and leads to a premature termination codon 98 amino acids downstream. This al teration is then predicted to lead to a truncated or absent protein. Biallelic l oss of function in the TULP1 gene has been associated with retinal dystrophy (Le ber congenital amaurosis or juvenile retinitis pigmentosa). In summary, although additional studies are required to fully establish its clinical significance, t he p.Val286ArgfsX98 variant in TULP1 is likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at