1-202137966-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_138795.4(ARL8A):c.277G>A(p.Val93Met) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_138795.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARL8A | NM_138795.4 | c.277G>A | p.Val93Met | missense_variant, splice_region_variant | 3/7 | ENST00000272217.7 | |
ARL8A | NM_001256129.2 | c.277G>A | p.Val93Met | missense_variant, splice_region_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARL8A | ENST00000272217.7 | c.277G>A | p.Val93Met | missense_variant, splice_region_variant | 3/7 | 1 | NM_138795.4 | P1 | |
ARL8A | ENST00000614750.1 | c.277G>A | p.Val93Met | missense_variant, splice_region_variant | 3/6 | 3 | |||
ARL8A | ENST00000486225.1 | n.69G>A | splice_region_variant, non_coding_transcript_exon_variant | 1/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461764Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727172
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2023 | The c.277G>A (p.V93M) alteration is located in exon 3 (coding exon 3) of the ARL8A gene. This alteration results from a G to A substitution at nucleotide position 277, causing the valine (V) at amino acid position 93 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at