chr13-94576339-A-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_014305.4(TGDS):c.957T>C(p.Pro319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,603,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 1 hom. )
Consequence
TGDS
NM_014305.4 synonymous
NM_014305.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.142
Genes affected
TGDS (HGNC:20324): (TDP-glucose 4,6-dehydratase) The protein encoded by this gene is a member of the short-chain dehydrogenases/reductases (SDR) superfamily, and is thought to contain a nicotinamide adenine dinucleotide (NAD) binding domain. This large SDR family of enzymes is involved in the metabolism of a variety of compounds, including prostaglandins, retinoids, lipids, steroid hormones, and xenobiotics. Mutations in this gene have been associated with Catel-Manzke syndrome, which is characterized by Pierre Robin sequence, and radial deviation of the index finger due to the presence of an accessory bone between the index finger and its proximal phalanx. Pierre Robin sequence is defined by an undersized jaw, backwards displacement of the tongue base that causes an obstruction of the airways, and can also be associated with a cleft palate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 13-94576339-A-G is Benign according to our data. Variant chr13-94576339-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1575281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.142 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGDS | NM_014305.4 | c.957T>C | p.Pro319= | synonymous_variant | 11/12 | ENST00000261296.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGDS | ENST00000261296.7 | c.957T>C | p.Pro319= | synonymous_variant | 11/12 | 1 | NM_014305.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 24AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000110 AC: 27AN: 244798Hom.: 0 AF XY: 0.0000983 AC XY: 13AN XY: 132242
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GnomAD4 exome AF: 0.000213 AC: 309AN: 1451346Hom.: 1 Cov.: 30 AF XY: 0.000205 AC XY: 148AN XY: 721696
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GnomAD4 genome ? AF: 0.000158 AC: 24AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74452
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
TGDS-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at