rs768701595
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_001252024.2(TRPM1):c.1263G>A(p.Pro421=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001252024.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM1 | NM_001252024.2 | c.1263G>A | p.Pro421= | splice_region_variant, synonymous_variant | 11/28 | ENST00000256552.11 | |
TRPM1 | NM_001252020.2 | c.1314G>A | p.Pro438= | splice_region_variant, synonymous_variant | 10/27 | ||
TRPM1 | NM_002420.6 | c.1197G>A | p.Pro399= | splice_region_variant, synonymous_variant | 10/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM1 | ENST00000256552.11 | c.1263G>A | p.Pro421= | splice_region_variant, synonymous_variant | 11/28 | 1 | NM_001252024.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249324Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135276
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461338Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727008
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74488
ClinVar
Submissions by phenotype
Congenital stationary night blindness 1C Pathogenic:1Uncertain:3
Uncertain significance, flagged submission | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Nov 02, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Equipe Genetique des Anomalies du Developpement, Université de Bourgogne | Sep 11, 2022 | This variant was observed with a CNV - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | reference population | Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center | Mar 18, 2016 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Dec 17, 2022 | - - |
Congenital stationary night blindness Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Sharon lab, Hadassah-Hebrew University Medical Center | Jun 23, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at