rs5925234

Variant names:

• chrX-152848710-T-C
• rs5925234
• NM_015922.3:c.109-1555T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-152848710-T-C
• chrX-152848710-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015922.3(NSDHL):​c.109-1555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (28613 hom., 28631 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: NSDHL NM_015922.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 1 publications found

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]

NSDHL Gene-Disease associations (from GenCC):

• CHILD syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, G2P
• CK syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSDHL	NM_015922.3	c.109-1555T>C		intron_variant	Intron 2 of 7	ENST00000370274.8	NP_057006.1
NSDHL	NM_001129765.2	c.109-1555T>C		intron_variant	Intron 3 of 8		NP_001123237.1
NSDHL	NM_001441099.1	c.109-1555T>C		intron_variant	Intron 4 of 9		NP_001428028.1
NSDHL	XM_017029564.2	c.157-1555T>C		intron_variant	Intron 2 of 7		XP_016885053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSDHL	ENST00000370274.8	c.109-1555T>C		intron_variant	Intron 2 of 7	1	NM_015922.3	ENSP00000359297.3
NSDHL	ENST00000440023.5	c.109-1555T>C		intron_variant	Intron 3 of 8	5		ENSP00000391854.1
NSDHL	ENST00000432467.1	c.109-1555T>C		intron_variant	Intron 3 of 7	3		ENSP00000396266.1

Frequencies

GnomAD3 genomes AF: 0.859 AC: 95230 AN: 110858 Hom.: 28619 Cov.: 23

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.960

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.878

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.866

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.859 AC: 95285 AN: 110912 Hom.: 28613 Cov.: 23 AF XY: 0.864 AC XY: 28631 AN XY: 33130

African (AFR) AF: 0.812 AC: 24693 AN: 30414

American (AMR) AF: 0.917 AC: 9573 AN: 10434

Ashkenazi Jewish (ASJ) AF: 0.919 AC: 2431 AN: 2644

East Asian (EAS) AF: 0.913 AC: 3214 AN: 3519

South Asian (SAS) AF: 0.930 AC: 2414 AN: 2595

European-Finnish (FIN) AF: 0.841 AC: 4985 AN: 5928

Middle Eastern (MID) AF: 0.870 AC: 187 AN: 215

European-Non Finnish (NFE) AF: 0.865 AC: 45818 AN: 52964

Other (OTH) AF: 0.867 AC: 1317 AN: 1519

Alfa AF: 0.869 Hom.: 57522

Bravo AF: 0.864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.0
DANN	Benign	0.40
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5925234; hg19: chrX-152017254;