rs104894902

Positions:

• chrX-152865903-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

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

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Child syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 14, 2000

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	35
DANN	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.98	D
MutationTaster	Benign	1.0	A;A
Vest4		0.95
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs104894902; hg19: chrX-152034447;