rs104894902
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015922.3(NSDHL):c.628C>T(p.Gln210Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 24)
Consequence
NSDHL
NM_015922.3 stop_gained
NM_015922.3 stop_gained
Scores
3
1
1
Clinical Significance
Conservation
PhyloP100: 5.00
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 Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-152865903-C-T is Pathogenic according to our data. Variant chrX-152865903-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 11428.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSDHL | NM_015922.3 | c.628C>T | p.Gln210Ter | stop_gained | 6/8 | ENST00000370274.8 | |
NSDHL | NM_001129765.2 | c.628C>T | p.Gln210Ter | stop_gained | 7/9 | ||
NSDHL | XM_017029564.2 | c.676C>T | p.Gln226Ter | stop_gained | 6/8 | ||
NSDHL | XM_011531178.3 | c.628C>T | p.Gln210Ter | stop_gained | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSDHL | ENST00000370274.8 | c.628C>T | p.Gln210Ter | stop_gained | 6/8 | 1 | NM_015922.3 | P1 | |
NSDHL | ENST00000440023.5 | c.628C>T | p.Gln210Ter | stop_gained | 7/9 | 5 | P1 | ||
NSDHL | ENST00000432467.1 | c.628C>T | p.Gln210Ter | stop_gained | 7/8 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Child syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 14, 2000 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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