NM_001252024.2:c.3171T>A
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate
The NM_001252024.2(TRPM1):c.3171T>A(p.Tyr1057*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,808 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 (★). Synonymous variant affecting the same amino acid position (i.e. Y1057Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001252024.2 stop_gained
Scores
Clinical Significance
Conservation
Publications
- congenital stationary night blindness 1CInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- TRPM1-related retinopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- congenital stationary night blindnessInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461808Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 727212 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Congenital stationary night blindness 1C Pathogenic:1
- -
not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Tyr1035*) in the TRPM1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRPM1 are known to be pathogenic (PMID: 19896113, 19966281, 20300565). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with night blindness (PMID: 19878917). ClinVar contains an entry for this variant (Variation ID: 6225). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at