NM_007231.5:c.145A>G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_007231.5(SLC6A14):āc.145A>Gā(p.Met49Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000307 in 1,205,864 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Consequence
NM_007231.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111887Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34031
GnomAD3 exomes AF: 0.00000548 AC: 1AN: 182337Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 66809
GnomAD4 exome AF: 0.0000320 AC: 35AN: 1093977Hom.: 0 Cov.: 29 AF XY: 0.0000223 AC XY: 8AN XY: 359433
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111887Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34031
ClinVar
Submissions by phenotype
not provided Uncertain:1
The SLC6A14 p.Met49Val variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs369863561) and in 1 of 182337 chromosomes at a frequency of 0.000005 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following population: European (non-Finnish) in 1 of 81642 chromosomes (freq:0.00001225); it was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), Other, and South Asian populations. The p.Met49 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The p.Met49Val variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at