chr10-69572882-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_020999.4(NEUROG3):c.162C>A(p.Cys54Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020999.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEUROG3 | NM_020999.4 | c.162C>A | p.Cys54Ter | stop_gained | 2/2 | ENST00000242462.5 | |
NEUROG3 | XM_017016280.2 | c.162C>A | p.Cys54Ter | stop_gained | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEUROG3 | ENST00000242462.5 | c.162C>A | p.Cys54Ter | stop_gained | 2/2 | 1 | NM_020999.4 | P1 | |
ENST00000685746.2 | upstream_gene_variant |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000418 AC: 1AN: 239186Hom.: 0 AF XY: 0.00000765 AC XY: 1AN XY: 130742
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457334Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 724888
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Congenital malabsorptive diarrhea 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 15, 2016 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 14, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 435975). This premature translational stop signal has been observed in individual(s) with clinical features of congenital malabsorptive diarrhea (Invitae). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Cys54*) in the NEUROG3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 161 amino acid(s) of the NEUROG3 protein. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at