X-152869048-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015922.3(NSDHL):c.1054C>T(p.Leu352Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,210,785 control chromosomes in the GnomAD database, including 23 homozygotes. There are 2,137 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 0.0045 ( 1 hom., 153 hem., cov: 23)

Exomes 𝑓: 0.0059 ( 22 hom. 1984 hem. )

Consequence

NSDHL
NM_015922.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.34

Publications

0 publications found

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 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

NSDHL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant X-152869048-C-T is Benign according to our data. Variant chrX-152869048-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 159448.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.34 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00454 (512/112688) while in subpopulation NFE AF = 0.0071 (378/53264). AF 95% confidence interval is 0.00651. There are 1 homozygotes in GnomAd4. There are 153 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 153 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSDHL	NM_015922.3 link	c.1054C>T	p.Leu352Leu	synonymous_variant	Exon 8 of 8	ENST00000370274.8	NP_057006.1	Q15738A0A384NPZ7
NSDHL	NM_001129765.2 link	c.1054C>T	p.Leu352Leu	synonymous_variant	Exon 9 of 9		NP_001123237.1	Q15738A0A384NPZ7
NSDHL	NM_001441099.1 link	c.1054C>T	p.Leu352Leu	synonymous_variant	Exon 10 of 10		NP_001428028.1
NSDHL	XM_017029564.2 link	c.1102C>T	p.Leu368Leu	synonymous_variant	Exon 8 of 8		XP_016885053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSDHL	ENST00000370274.8 link	c.1054C>T	p.Leu352Leu	synonymous_variant	Exon 8 of 8	1	NM_015922.3	ENSP00000359297.3		Q15738
NSDHL	ENST00000440023.5 link	c.1054C>T	p.Leu352Leu	synonymous_variant	Exon 9 of 9	5		ENSP00000391854.1		Q15738

Frequencies

GnomAD3 genomes

AF:

0.00456

AC:

514

AN:

112637

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000903

Gnomad AMI

AF:

0.00873

Gnomad AMR

AF:

0.00476

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00183

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0125

Gnomad NFE

AF:

0.00710

Gnomad OTH

AF:

0.00462

GnomAD2 exomes

AF:

0.00477

AC:

874

AN:

183245

AF XY:

0.00447

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.00511

Gnomad ASJ exome

AF:

0.00815

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00156

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.00929

GnomAD4 exome

AF:

0.00589

AC:

6468

AN:

1098097

Hom.:

Cov.:

AF XY:

0.00546

AC XY:

1984

AN XY:

363453

show subpopulations

African (AFR)

AF:

0.000720

AC:

AN:

26399

American (AMR)

AF:

0.00491

AC:

173

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00820

AC:

159

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.00129

AC:

AN:

54141

European-Finnish (FIN)

AF:

0.00220

AC:

AN:

40511

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00667

AC:

5619

AN:

842022

Other (OTH)

AF:

0.00631

AC:

291

AN:

46092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

267

534

801

1068

1335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00454

AC:

512

AN:

112688

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

153

AN XY:

34848

show subpopulations

African (AFR)

AF:

0.000901

AC:

AN:

31083

American (AMR)

AF:

0.00476

AC:

AN:

10717

Ashkenazi Jewish (ASJ)

AF:

0.00982

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3574

South Asian (SAS)

AF:

0.00183

AC:

AN:

2727

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

6235

Middle Eastern (MID)

AF:

0.00457

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00710

AC:

378

AN:

53264

Other (OTH)

AF:

0.00457

AC:

AN:

1533

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00544

Hom.:

Bravo

AF:

0.00463

EpiCase

AF:

0.00834

EpiControl

AF:

0.00818

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 11, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 02, 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

- -

not specified

Benign:2

Dec 11, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 08, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Child syndrome;C3151781:CK syndrome

Benign:1

Jul 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Connective tissue disorder

Benign:1

Sep 01, 2019

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

CK syndrome

Benign:1

May 18, 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

-0.71

CADD

Benign

5.9

(source)

DANN

Benign

0.57

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over