chr12-8848913-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_144670.6(A2ML1):c.2027G>A(p.Arg676Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,610,310 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R676W) has been classified as Likely benign.
Frequency
Consequence
NM_144670.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
A2ML1 | NM_144670.6 | c.2027G>A | p.Arg676Gln | missense_variant, splice_region_variant | 16/36 | ENST00000299698.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
A2ML1 | ENST00000299698.12 | c.2027G>A | p.Arg676Gln | missense_variant, splice_region_variant | 16/36 | 1 | NM_144670.6 | P1 | |
A2ML1 | ENST00000541459.5 | c.677G>A | p.Arg226Gln | missense_variant, splice_region_variant | 5/25 | 2 | |||
A2ML1 | ENST00000539547.5 | c.554G>A | p.Arg185Gln | missense_variant, splice_region_variant | 5/25 | 2 | |||
A2ML1 | ENST00000545692.1 | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000664 AC: 101AN: 152132Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000208 AC: 51AN: 244686Hom.: 0 AF XY: 0.0000979 AC XY: 13AN XY: 132730
GnomAD4 exome AF: 0.0000844 AC: 123AN: 1458058Hom.: 0 Cov.: 30 AF XY: 0.0000731 AC XY: 53AN XY: 725204
GnomAD4 genome AF: 0.000663 AC: 101AN: 152252Hom.: 1 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74464
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 12, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at