chr20-58891864-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000516.7(GNAS):c.138G>A(p.Leu46=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000377 in 1,060,800 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 predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L46L) has been classified as Likely benign.
Frequency
Consequence
NM_000516.7 splice_region, synonymous
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 |
---|---|---|---|---|---|---|---|
GNAS | NM_000516.7 | c.138G>A | p.Leu46= | splice_region_variant, synonymous_variant | 1/13 | ENST00000371085.8 | |
GNAS | NM_016592.5 | c.*43-3748G>A | intron_variant | ENST00000371075.7 | |||
GNAS | NM_080425.4 | c.2069-3748G>A | intron_variant | ENST00000371100.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GNAS | ENST00000371085.8 | c.138G>A | p.Leu46= | splice_region_variant, synonymous_variant | 1/13 | 1 | NM_000516.7 | ||
GNAS | ENST00000371075.7 | c.*43-3748G>A | intron_variant | 1 | NM_016592.5 | ||||
GNAS | ENST00000371100.9 | c.2069-3748G>A | intron_variant | 5 | NM_080425.4 |
Frequencies
GnomAD3 genomes Cov.: 28
GnomAD3 exomes AF: 0.00000553 AC: 1AN: 180912Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 102058
GnomAD4 exome AF: 0.00000377 AC: 4AN: 1060800Hom.: 0 Cov.: 31 AF XY: 0.00000383 AC XY: 2AN XY: 521512
GnomAD4 genome Cov.: 28
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 14, 2015 | - - |
GNAS-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 07, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at