6-84062888-T-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_138409.4(MRAP2):c.128-5T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_138409.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MRAP2 | NM_138409.4 | c.128-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000257776.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MRAP2 | ENST00000257776.5 | c.128-5T>G | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_138409.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000115 AC: 29AN: 251430Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135904
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461814Hom.: 1 Cov.: 31 AF XY: 0.0000839 AC XY: 61AN XY: 727214
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74380
ClinVar
Submissions by phenotype
MRAP2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 08, 2024 | The MRAP2 c.128-5T>G variant is predicted to interfere with splicing. This variant is predicted to alter splicing based on available splicing prediction programs (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.095% of alleles in individuals of South Asian descent in gnomAD. Of note, loss of function variants, specifically splicing variants, have not commonly been reported in the MRAP2 gene. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at