rs587784222

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_ModeratePM2PP5_Moderate

The NM_015922.3(NSDHL):​c.1114delG​(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

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: -0.172
Variant links:
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.

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 0.00713 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 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 rank MANE Protein UniProt
NSDHLNM_015922.3 linkc.1114delG p.Val372SerfsTer32 frameshift_variant Exon 8 of 8 ENST00000370274.8 NP_057006.1 Q15738A0A384NPZ7
NSDHLNM_001129765.2 linkc.1114delG p.Val372SerfsTer32 frameshift_variant Exon 9 of 9 NP_001123237.1 Q15738A0A384NPZ7
NSDHLXM_017029564.2 linkc.1162delG p.Val388SerfsTer32 frameshift_variant Exon 8 of 8 XP_016885053.1
NSDHLXM_011531178.3 linkc.1114delG p.Val372SerfsTer32 frameshift_variant Exon 10 of 10 XP_011529480.1 Q15738A0A384NPZ7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NSDHLENST00000370274.8 linkc.1114delG p.Val372SerfsTer32 frameshift_variant Exon 8 of 8 1 NM_015922.3 ENSP00000359297.3 Q15738
NSDHLENST00000440023.5 linkc.1114delG p.Val372SerfsTer32 frameshift_variant Exon 9 of 9 5 ENSP00000391854.1 Q15738

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
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
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs587784222; hg19: chrX-152037649; API