rs587784222
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_015922.3(NSDHL):c.1114del(p.Val372SerfsTer32) 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 Likely pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Consequence
NSDHL
NM_015922.3 frameshift
NM_015922.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.172
Genes affected
NSDHL (HGNC:13398): (NAD(P) dependent steroid dehydrogenase-like) The protein encoded by this gene is localized in the endoplasmic reticulum and is involved in cholesterol biosynthesis. Mutations in this gene are associated with CHILD syndrome, which is a X-linked dominant disorder of lipid metabolism with disturbed cholesterol biosynthesis, and typically lethal in males. Alternatively spliced transcript variants with differing 5' UTR have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 430 codons.
PP5
?
Variant X-152869105-AG-A is Pathogenic according to our data. Variant chrX-152869105-AG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 159449.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSDHL | NM_015922.3 | c.1114del | p.Val372SerfsTer32 | frameshift_variant | 8/8 | ENST00000370274.8 | |
NSDHL | NM_001129765.2 | c.1114del | p.Val372SerfsTer32 | frameshift_variant | 9/9 | ||
NSDHL | XM_017029564.2 | c.1162del | p.Val388SerfsTer32 | frameshift_variant | 8/8 | ||
NSDHL | XM_011531178.3 | c.1114del | p.Val372SerfsTer32 | frameshift_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSDHL | ENST00000370274.8 | c.1114del | p.Val372SerfsTer32 | frameshift_variant | 8/8 | 1 | NM_015922.3 | P1 | |
NSDHL | ENST00000440023.5 | c.1114del | p.Val372SerfsTer32 | frameshift_variant | 9/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Child syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 08, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at