rs61744220
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_144670.6(A2ML1):āc.1109T>Cā(p.Phe370Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00494 in 1,614,056 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_144670.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
A2ML1 | NM_144670.6 | c.1109T>C | p.Phe370Ser | missense_variant | 11/36 | ENST00000299698.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
A2ML1 | ENST00000299698.12 | c.1109T>C | p.Phe370Ser | missense_variant | 11/36 | 1 | NM_144670.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0263 AC: 4003AN: 152116Hom.: 176 Cov.: 32
GnomAD3 exomes AF: 0.00670 AC: 1671AN: 249494Hom.: 86 AF XY: 0.00464 AC XY: 628AN XY: 135366
GnomAD4 exome AF: 0.00271 AC: 3965AN: 1461822Hom.: 177 Cov.: 31 AF XY: 0.00226 AC XY: 1644AN XY: 727214
GnomAD4 genome ? AF: 0.0263 AC: 4007AN: 152234Hom.: 177 Cov.: 32 AF XY: 0.0254 AC XY: 1892AN XY: 74454
ClinVar
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:2Other:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided, no classification provided | literature only | Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 06, 2017 | Variant summary: The A2ML1 c.1109T>C (p.Phe370Ser) variant involves the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 967/120708 control chromosomes (48 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.089778 (880/9802). This frequency is about 22444 times the estimated maximal expected allele frequency of a pathogenic A2ML1 variant (0.000004), thus it is a benign common polymorphism found primarily in the populations of African origin. In addition, one clinical diagnostic laboratory (via ClinVar) has classified this variant as benign. Taken together, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at