X-152846040-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015922.3(NSDHL):c.-43-242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 112,629 control chromosomes in the GnomAD database, including 182 homozygotes. There are 2,253 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.064 (182 hom., 2253 hem., cov: 23)
• Consequence: NSDHL NM_015922.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0350

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=-0.83).
• BP6: Variant X-152846040-C-T is Benign according to our data. Variant chrX-152846040-C-T is described in ClinVar as [Benign]. Clinvar id is 1247815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSDHL	NM_015922.3	c.-43-242C>T		intron_variant		ENST00000370274.8
NSDHL	NM_001129765.2	c.-43-242C>T		intron_variant
NSDHL	XM_011531178.3	c.-43-242C>T		intron_variant
NSDHL	XM_017029564.2	c.6-242C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSDHL	ENST00000370274.8	c.-43-242C>T		intron_variant		1	NM_015922.3	P1
NSDHL	ENST00000432467.1	c.-43-242C>T		intron_variant		3
NSDHL	ENST00000440023.5	c.-43-242C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 7157 AN: 112574 Hom.: 181 Cov.: 23 AF XY: 0.0647 AC XY: 2248 AN XY: 34744

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.0204

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.0685

Gnomad EAS AF: 0.0944

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0389

Gnomad MID AF: 0.0720

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0672

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

GnomAD4 genome AF: 0.0635 AC: 7157 AN: 112629 Hom.: 182 Cov.: 23 AF XY: 0.0647 AC XY: 2253 AN XY: 34809

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.0942

Gnomad4 ASJ AF: 0.0685

Gnomad4 EAS AF: 0.0939

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0389

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0650

Alfa AF: 0.0606 Hom.: 430

Bravo AF: 0.0711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0
Dann	Benign	0.61

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: rs6627272; hg19: chrX-152014584;