12-49588449-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032130.3(FAM186B):c.2534+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,460 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_032130.3 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAM186B | NM_032130.3 | c.2534+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000257894.2 | NP_115506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FAM186B | ENST00000257894.2 | c.2534+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_032130.3 | ENSP00000257894 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247544Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133662
GnomAD4 exome AF: 6.87e-7 AC: 1AN: 1456460Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 723778
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 23, 2021 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. This variant has not been reported in the literature in individuals affected with FAM186B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change falls in intron 6 of the FAM186B gene. It does not directly change the encoded amino acid sequence of the FAM186B protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at