11-62613296-GC-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2
The NM_000327.4(ROM1):c.19delC(p.Leu7TrpfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,607,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000327.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ROM1 | ENST00000278833.4 | c.19delC | p.Leu7TrpfsTer40 | frameshift_variant | Exon 1 of 3 | 1 | NM_000327.4 | ENSP00000278833.3 | ||
ROM1 | ENST00000534093.5 | c.-38-958delC | intron_variant | Intron 1 of 2 | 2 | ENSP00000432151.1 | ||||
ROM1 | ENST00000525801.1 | c.-38-958delC | intron_variant | Intron 1 of 1 | 3 | ENSP00000433566.1 | ||||
ROM1 | ENST00000525947.1 | c.-517delC | upstream_gene_variant | 3 | ENSP00000432983.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 34
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1454790Hom.: 0 Cov.: 77 AF XY: 0.00000138 AC XY: 1AN XY: 723412
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152228Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74376
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change creates a premature translational stop signal (p.Leu7Trpfs*40) in the ROM1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ROM1 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ROM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1942158). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at