rs121909833

Positions:

• chrX-152867576-GGAA-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_015922.3(NSDHL):​c.696_698delGAA​(p.Lys232del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NSDHL NM_015922.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 4.98

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_015922.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant X-152867576-GGAA-G is Pathogenic according to our data. Variant chrX-152867576-GGAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 21268.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSDHL	NM_015922.3	c.696_698delGAA	p.Lys232del	disruptive_inframe_deletion	7/8	ENST00000370274.8	NP_057006.1
NSDHL	NM_001129765.2	c.696_698delGAA	p.Lys232del	disruptive_inframe_deletion	8/9		NP_001123237.1
NSDHL	XM_017029564.2	c.744_746delGAA	p.Lys248del	disruptive_inframe_deletion	7/8		XP_016885053.1
NSDHL	XM_011531178.3	c.696_698delGAA	p.Lys232del	disruptive_inframe_deletion	9/10		XP_011529480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSDHL	ENST00000370274.8	c.696_698delGAA	p.Lys232del	disruptive_inframe_deletion	7/8	1	NM_015922.3	ENSP00000359297.3
NSDHL	ENST00000440023.5	c.696_698delGAA	p.Lys232del	disruptive_inframe_deletion	8/9	5		ENSP00000391854.1
NSDHL	ENST00000432467.1	c.696_698delGAA	p.Lys232del	disruptive_inframe_deletion	8/8	3		ENSP00000396266.1

Frequencies

GnomAD3 genomes Cov.: 23

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 23

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

CK syndrome Pathogenic:1 Other:1

Pathogenic, no assertion criteria provided	literature only	OMIM	Dec 10, 2010	- -
not provided, no classification provided	clinical testing	GeneReviews	-	- -

Computational scores

Source: dbNSFP v4.3

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: rs121909833; hg19: chrX-152036120;