2-69507505-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014911.5(AAK1):āc.2080A>Gā(p.Thr694Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T694M) has been classified as Likely benign.
Frequency
Consequence
NM_014911.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AAK1 | NM_014911.5 | c.2080A>G | p.Thr694Ala | missense_variant | 15/22 | ENST00000409085.9 | NP_055726.4 | |
AAK1 | NM_001371575.1 | c.2080A>G | p.Thr694Ala | missense_variant | 15/21 | NP_001358504.1 | ||
AAK1 | NM_001371577.1 | c.1980+1752A>G | intron_variant | NP_001358506.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AAK1 | ENST00000409085.9 | c.2080A>G | p.Thr694Ala | missense_variant | 15/22 | 5 | NM_014911.5 | ENSP00000386456.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000406 AC: 1AN: 246514Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133642
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460374Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726290
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2024 | The c.2080A>G (p.T694A) alteration is located in exon 15 (coding exon 14) of the AAK1 gene. This alteration results from a A to G substitution at nucleotide position 2080, causing the threonine (T) at amino acid position 694 to be replaced by an alanine (A). 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