chrX-49199016-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_003179.3(SYP):c.54G>A(p.Gln18Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,209,653 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Consequence
NM_003179.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000895 AC: 1AN: 111744Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1AN XY: 33886
GnomAD3 exomes AF: 0.0000553 AC: 10AN: 180958Hom.: 0 AF XY: 0.0000455 AC XY: 3AN XY: 65966
GnomAD4 exome AF: 0.00000911 AC: 10AN: 1097909Hom.: 0 Cov.: 30 AF XY: 0.00000826 AC XY: 3AN XY: 363267
GnomAD4 genome AF: 0.00000895 AC: 1AN: 111744Hom.: 0 Cov.: 22 AF XY: 0.0000295 AC XY: 1AN XY: 33886
ClinVar
Submissions by phenotype
not provided Benign:1
The SYP p.Gln18Gln variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs781815856) and ClinVar (classified as likely benign by Illumina for intellectual disability). The variant was identified in control databases in 10 of 202818 chromosomes (3 hemizygous) at a frequency of 0.000049 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 9 of 14798 chromosomes (freq: 0.000608) and Other in 1 of 5261 chromosomes (freq: 0.00019), but not in the African, Latino, Ashkenazi Jewish, European (Finnish), European (non-Finnish), and South Asian populations. The p.Gln18Gln variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, only 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at