19-49293890-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014037.3(SLC6A16):c.1555G>A(p.Gly519Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G519V) has been classified as Uncertain significance.
Frequency
Consequence
NM_014037.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC6A16 | ENST00000335875.9 | c.1555G>A | p.Gly519Ser | missense_variant | Exon 9 of 12 | 5 | NM_014037.3 | ENSP00000338627.3 | ||
SLC6A16 | ENST00000454748.7 | c.1555G>A | p.Gly519Ser | missense_variant | Exon 9 of 11 | 1 | ENSP00000404022.2 | |||
SLC6A16 | ENST00000598828.1 | c.190G>A | p.Gly64Ser | missense_variant | Exon 3 of 5 | 2 | ENSP00000469885.1 | |||
SLC6A16 | ENST00000598221.1 | n.411G>A | non_coding_transcript_exon_variant | Exon 3 of 4 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249542Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135388
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727222
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1555G>A (p.G519S) alteration is located in exon 9 (coding exon 8) of the SLC6A16 gene. This alteration results from a G to A substitution at nucleotide position 1555, causing the glycine (G) at amino acid position 519 to be replaced by a serine (S). 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