X-152850288-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_015922.3(NSDHL):c.132T>G(p.Gly44Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.84 ( 27281 hom., 27862 hem., cov: 23)

Exomes 𝑓: 0.87 ( 279620 hom. 318527 hem. )

Failed GnomAD Quality Control

Consequence

NSDHL
NM_015922.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.673

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-152850288-T-G is Benign according to our data. Variant chrX-152850288-T-G is described in ClinVar as [Benign]. Clinvar id is 159450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-152850288-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.673 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSDHL	NM_015922.3 link	c.132T>G	p.Gly44Gly	synonymous_variant	Exon 3 of 8	ENST00000370274.8	NP_057006.1	Q15738A0A384NPZ7
NSDHL	NM_001129765.2 link	c.132T>G	p.Gly44Gly	synonymous_variant	Exon 4 of 9		NP_001123237.1	Q15738A0A384NPZ7
NSDHL	XM_017029564.2 link	c.180T>G	p.Gly60Gly	synonymous_variant	Exon 3 of 8		XP_016885053.1
NSDHL	XM_011531178.3 link	c.132T>G	p.Gly44Gly	synonymous_variant	Exon 5 of 10		XP_011529480.1	Q15738A0A384NPZ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NSDHL	ENST00000370274.8 link	c.132T>G	p.Gly44Gly	synonymous_variant	Exon 3 of 8	1	NM_015922.3	ENSP00000359297.3	Q15738
NSDHL	ENST00000440023.5 link	c.132T>G	p.Gly44Gly	synonymous_variant	Exon 4 of 9	5		ENSP00000391854.1	Q15738
NSDHL	ENST00000432467.1 link	c.132T>G	p.Gly44Gly	synonymous_variant	Exon 4 of 8	3		ENSP00000396266.1	C9JDR0

Frequencies

GnomAD3 genomes

AF:

0.838

AC:

92769

AN:

110674

Hom.:

27288

Cov.:

AF XY:

0.845

AC XY:

27795

AN XY:

32886

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.960

Gnomad AMR

AF:

0.909

Gnomad ASJ

AF:

0.920

Gnomad EAS

AF:

0.915

Gnomad SAS

AF:

0.930

Gnomad FIN

AF:

0.841

Gnomad MID

AF:

0.870

Gnomad NFE

AF:

0.865

Gnomad OTH

AF:

0.856

GnomAD3 exomes

AF:

0.882

AC:

161742

AN:

183420

Hom.:

44885

AF XY:

0.886

AC XY:

60110

AN XY:

67866

show subpopulations

Gnomad AFR exome

AF:

0.746

Gnomad AMR exome

AF:

0.940

Gnomad ASJ exome

AF:

0.918

Gnomad EAS exome

AF:

0.916

Gnomad SAS exome

AF:

0.941

Gnomad FIN exome

AF:

0.852

Gnomad NFE exome

AF:

0.867

Gnomad OTH exome

AF:

0.880

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.874

AC:

959053

AN:

1097942

Hom.:

279620

Cov.:

AF XY:

0.877

AC XY:

318527

AN XY:

363394

show subpopulations

Gnomad4 AFR exome

AF:

0.744

Gnomad4 AMR exome

AF:

0.937

Gnomad4 ASJ exome

AF:

0.915

Gnomad4 EAS exome

AF:

0.945

Gnomad4 SAS exome

AF:

0.939

Gnomad4 FIN exome

AF:

0.847

Gnomad4 NFE exome

AF:

0.868

Gnomad4 OTH exome

AF:

0.872

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.838

AC:

92823

AN:

110730

Hom.:

27281

Cov.:

AF XY:

0.846

AC XY:

27862

AN XY:

32952

show subpopulations

Gnomad4 AFR

AF:

0.740

Gnomad4 AMR

AF:

0.909

Gnomad4 ASJ

AF:

0.920

Gnomad4 EAS

AF:

0.915

Gnomad4 SAS

AF:

0.929

Gnomad4 FIN

AF:

0.841

Gnomad4 NFE

AF:

0.865

Gnomad4 OTH

AF:

0.857

Alfa

AF:

0.871

Hom.:

15588

Bravo

AF:

0.841

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 04, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 02, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Child syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CK syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.9

DANN

Benign

0.54

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