Menu
GeneBe

rs387906835

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_003322.6(TULP1):c.1204G>T(p.Glu402Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

TULP1
NM_003322.6 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 7.86
Variant links:
Genes affected
TULP1 (HGNC:12423): (TUB like protein 1) This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15. [provided by RefSeq, Nov 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-35503757-C-A is Pathogenic according to our data. Variant chr6-35503757-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 30260.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-35503757-C-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TULP1NM_003322.6 linkuse as main transcriptc.1204G>T p.Glu402Ter stop_gained 12/15 ENST00000229771.11
LOC124901309XR_007059561.1 linkuse as main transcriptn.76-4470C>A intron_variant, non_coding_transcript_variant
TULP1NM_001289395.2 linkuse as main transcriptc.1045G>T p.Glu349Ter stop_gained 11/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TULP1ENST00000229771.11 linkuse as main transcriptc.1204G>T p.Glu402Ter stop_gained 12/151 NM_003322.6 P4O00294-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Leber congenital amaurosis 15 Pathogenic:2
Pathogenic, no assertion criteria providedliterature onlyOMIMApr 01, 2004- -
Pathogenic, no assertion criteria providedresearchLaboratory of Genetics in Ophthalmology, Institut Imagine-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.68
D
BayesDel_noAF
Pathogenic
0.66
Cadd
Pathogenic
43
Dann
Uncertain
1.0
Eigen
Pathogenic
1.1
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
1.0
D
MutationTaster
Benign
1.0
A;A
Vest4
0.90
GERP RS
4.8

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.18
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs387906835; hg19: chr6-35471534; API