chr3-57198229-TC-T
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Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_003865.3(HESX1):c.525del(p.Asn178IlefsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A175A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
HESX1
NM_003865.3 frameshift
NM_003865.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -1.93
Genes affected
HESX1 (HGNC:4877): (HESX homeobox 1) This gene encodes a conserved homeobox protein that is a transcriptional repressor in the developing forebrain and pituitary gland. Mutations in this gene are associated with septooptic dysplasia, HESX1-related growth hormone deficiency, and combined pituitary hormone deficiency. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0591 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-57198229-TC-T is Pathogenic according to our data. Variant chr3-57198229-TC-T is described in ClinVar as [Pathogenic]. Clinvar id is 7696.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HESX1 | NM_003865.3 | c.525del | p.Asn178IlefsTer10 | frameshift_variant | 4/4 | ENST00000295934.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HESX1 | ENST00000295934.8 | c.525del | p.Asn178IlefsTer10 | frameshift_variant | 4/4 | 1 | NM_003865.3 | P1 | |
HESX1 | ENST00000647958.1 | c.525del | p.Asn178IlefsTer10 | frameshift_variant | 7/7 | P1 | |||
HESX1 | ENST00000473921.2 | c.423del | p.Asn144IlefsTer10 | frameshift_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1460504Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726566
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1460504
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30
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726566
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Septo-optic dysplasia sequence Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2003 | - - |
Computational scores
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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
Publications
No publications associated with this variant yet.