Variant X-152850236-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015922.3(NSDHL):c.109-29T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00096 in 1,204,742 control chromosomes in the GnomAD database, including 12 homozygotes. There are 275 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 0.0051 ( 3 hom., 146 hem., cov: 24)

Exomes 𝑓: 0.00054 ( 9 hom. 129 hem. )

Consequence

NSDHL
NM_015922.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0590

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-152850236-T-G is Benign according to our data. Variant chrX-152850236-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1191540.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00505 (568/112376) while in subpopulation AFR AF= 0.017 (527/30951). AF 95% confidence interval is 0.0158. There are 3 homozygotes in gnomad4. There are 146 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
NSDHL	NM_015922.3 linkuse as main transcript	c.109-29T>G	intron_variant	ENST00000370274.8	NP_057006.1	Q15738A0A384NPZ7
NSDHL	NM_001129765.2 linkuse as main transcript	c.109-29T>G	intron_variant		NP_001123237.1	Q15738A0A384NPZ7
NSDHL	XM_017029564.2 linkuse as main transcript	c.157-29T>G	intron_variant		XP_016885053.1
NSDHL	XM_011531178.3 linkuse as main transcript	c.109-29T>G	intron_variant		XP_011529480.1	Q15738A0A384NPZ7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NSDHL	ENST00000370274.8 linkuse as main transcript	c.109-29T>G	intron_variant	1	NM_015922.3	ENSP00000359297.3	Q15738
NSDHL	ENST00000440023.5 linkuse as main transcript	c.109-29T>G	intron_variant	5		ENSP00000391854.1	Q15738
NSDHL	ENST00000432467.1 linkuse as main transcript	c.109-29T>G	intron_variant	3		ENSP00000396266.1	C9JDR0

Frequencies

GnomAD3 genomes

AF:

0.00506

AC:

568

AN:

112325

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

146

AN XY:

34483

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00599

GnomAD3 exomes

AF:

0.00147

AC:

270

AN:

183372

Hom.:

AF XY:

0.000796

AC XY:

AN XY:

67828

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000883

GnomAD4 exome

AF:

0.000539

AC:

589

AN:

1092366

Hom.:

Cov.:

AF XY:

0.000360

AC XY:

129

AN XY:

358172

show subpopulations

Gnomad4 AFR exome

AF:

0.0200

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000358

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.00505

AC:

568

AN:

112376

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

146

AN XY:

34544

show subpopulations

Gnomad4 AFR

AF:

0.0170

Gnomad4 AMR

AF:

0.00273

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00591

Alfa

AF:

0.00273

Hom.:

Bravo

AF:

0.00559

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over