chrX-70445329-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_021120.4(DLG3):c.128G>T(p.Gly43Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,167,472 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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. G43R) has been classified as Uncertain significance.
Frequency
Consequence
NM_021120.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLG3 | NM_021120.4 | c.128G>T | p.Gly43Val | missense_variant | 1/19 | ENST00000374360.8 | |
DLG3 | XM_006724625.3 | c.128G>T | p.Gly43Val | missense_variant | 1/20 | ||
DLG3 | XM_011530883.2 | c.128G>T | p.Gly43Val | missense_variant | 1/19 | ||
DLG3 | XM_006724626.3 | c.128G>T | p.Gly43Val | missense_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLG3 | ENST00000374360.8 | c.128G>T | p.Gly43Val | missense_variant | 1/19 | 1 | NM_021120.4 | ||
DLG3 | ENST00000194900.8 | c.128G>T | p.Gly43Val | missense_variant | 1/21 | 5 | P1 | ||
DLG3 | ENST00000463252.5 | n.194G>T | non_coding_transcript_exon_variant | 1/19 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000176 AC: 2AN: 113419Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35573
GnomAD3 exomes AF: 0.0000667 AC: 7AN: 104956Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 36114
GnomAD4 exome AF: 0.0000199 AC: 21AN: 1054004Hom.: 0 Cov.: 31 AF XY: 0.0000146 AC XY: 5AN XY: 343614
GnomAD4 genome ? AF: 0.0000176 AC: 2AN: 113468Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 35632
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 30, 2020 | The alteration results in an amino acid change:_x000D_ _x000D_ The c.128G>T (p.G43V) alteration is located in exon 1 (coding exon 1) of the DLG3 gene. This alteration results from a G to T substitution at nucleotide position 128, causing the glycine (G) at amino acid position 43 to be replaced by a valine (V). The alteration has been observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the DLG3 c.128G>T alteration was observed in 0.007% (7/104956) of total alleles studied, with a frequency of 0.08% (7/8476) in the East Asian subpopulation; no hemizygous males were observed. The alteration has been observed in affected individuals: _x000D_ _x000D_ This alteration was reported to be maternally inherited a hemizygous Chinese male with global developmental delay, including speech delay, and craniofacial findings (Huifang, 2016). The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.G43 amino acid is conserved in available vertebrate species. The alteration is predicted tolerated by in silico modeling:_x000D_ _x000D_ The p.G43V alteration is predicted to be tolerated by in silico analysis. 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