X-152846687-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015922.3(NSDHL):c.108+255G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.011 in 112,076 control chromosomes in the GnomAD database, including 24 homozygotes. There are 308 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.011 (24 hom., 308 hem., cov: 23)
• Consequence: NSDHL NM_015922.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-152846687-G-C is Benign according to our data. Variant chrX-152846687-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1215963.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1230/112076) while in subpopulation AFR AF= 0.0375 (1156/30842). AF 95% confidence interval is 0.0357. There are 24 homozygotes in gnomad4. There are 308 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSDHL	NM_015922.3	c.108+255G>C		intron_variant		ENST00000370274.8
NSDHL	NM_001129765.2	c.108+255G>C		intron_variant
NSDHL	XM_011531178.3	c.108+255G>C		intron_variant
NSDHL	XM_017029564.2	c.156+255G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSDHL	ENST00000370274.8	c.108+255G>C		intron_variant		1	NM_015922.3	P1
NSDHL	ENST00000432467.1	c.108+255G>C		intron_variant		3
NSDHL	ENST00000440023.5	c.108+255G>C		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1227 AN: 112026 Hom.: 23 Cov.: 23 AF XY: 0.00904 AC XY: 309 AN XY: 34198

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000743

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.0113

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

GnomAD4 genome AF: 0.0110 AC: 1230 AN: 112076 Hom.: 24 Cov.: 23 AF XY: 0.00899 AC XY: 308 AN XY: 34258

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.00491

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000745

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000376

Gnomad4 OTH AF: 0.0111

Alfa AF: 0.00783 Hom.: 18

Bravo AF: 0.0130

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 15, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.70
Dann	Benign	0.49

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: rs112413158; hg19: chrX-152015231;