11-9139708-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_015213.4(DENND5A):c.3827C>T(p.Thr1276Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T1276T) has been classified as Likely benign.
Frequency
Consequence
NM_015213.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DENND5A | NM_015213.4 | c.3827C>T | p.Thr1276Met | missense_variant | 23/23 | ENST00000328194.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DENND5A | ENST00000328194.8 | c.3827C>T | p.Thr1276Met | missense_variant | 23/23 | 1 | NM_015213.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250834Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135568
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461736Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727154
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 29, 2024 | The c.3827C>T (p.T1276M) alteration is located in exon 23 (coding exon 23) of the DENND5A gene. This alteration results from a C to T substitution at nucleotide position 3827, causing the threonine (T) at amino acid position 1276 to be replaced by a methionine (M). 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