rs200930841

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_015922.3(NSDHL):c.356G>A(p.Arg119Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000509 in 1,203,375 control chromosomes in the GnomAD database, including 1 homozygotes. There are 202 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., 17 hem., cov: 23)

Exomes 𝑓: 0.00050 ( 1 hom. 185 hem. )

Consequence

NSDHL
NM_015922.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.34

Publications

1 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12504587).

BP6

Variant X-152858858-G-A is Benign according to our data. Variant chrX-152858858-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 211750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000563 (63/111834) while in subpopulation AMR AF = 0.000758 (8/10550). AF 95% confidence interval is 0.000503. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Hemizygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NSDHL	NM_015922.3 link	c.356G>A	p.Arg119Lys	missense_variant	Exon 4 of 8	ENST00000370274.8	NP_057006.1	Q15738A0A384NPZ7
NSDHL	NM_001129765.2 link	c.356G>A	p.Arg119Lys	missense_variant	Exon 5 of 9		NP_001123237.1	Q15738A0A384NPZ7
NSDHL	NM_001441099.1 link	c.356G>A	p.Arg119Lys	missense_variant	Exon 6 of 10		NP_001428028.1
NSDHL	XM_017029564.2 link	c.404G>A	p.Arg135Lys	missense_variant	Exon 4 of 8		XP_016885053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NSDHL	ENST00000370274.8 link	c.356G>A	p.Arg119Lys	missense_variant	Exon 4 of 8	1	NM_015922.3	ENSP00000359297.3	Q15738
NSDHL	ENST00000440023.5 link	c.356G>A	p.Arg119Lys	missense_variant	Exon 5 of 9	5		ENSP00000391854.1	Q15738
NSDHL	ENST00000432467.1 link	c.356G>A	p.Arg119Lys	missense_variant	Exon 5 of 8	3		ENSP00000396266.1	C9JDR0

Frequencies

GnomAD3 genomes

AF:

0.000564

AC:

AN:

111780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000759

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.000656

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000677

Gnomad OTH

AF:

0.00199

GnomAD2 exomes

AF:

0.000523

AC:

AN:

183468

AF XY:

0.000648

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.000267

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000125

Gnomad NFE exome

AF:

0.000903

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000504

AC:

550

AN:

1091541

Hom.:

Cov.:

AF XY:

0.000518

AC XY:

185

AN XY:

357049

show subpopulations

African (AFR)

AF:

0.0000761

AC:

AN:

26296

American (AMR)

AF:

0.000284

AC:

AN:

35201

Ashkenazi Jewish (ASJ)

AF:

0.000258

AC:

AN:

19347

East Asian (EAS)

AF:

0.00

AC:

AN:

30176

South Asian (SAS)

AF:

0.000222

AC:

AN:

53987

European-Finnish (FIN)

AF:

0.000222

AC:

AN:

40534

Middle Eastern (MID)

AF:

0.00533

AC:

AN:

4127

European-Non Finnish (NFE)

AF:

0.000535

AC:

447

AN:

835992

Other (OTH)

AF:

0.000937

AC:

AN:

45881

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000563

AC:

AN:

111834

Hom.:

Cov.:

AF XY:

0.000500

AC XY:

AN XY:

34010

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

30763

American (AMR)

AF:

0.000758

AC:

AN:

10550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3561

South Asian (SAS)

AF:

0.000380

AC:

AN:

2630

European-Finnish (FIN)

AF:

0.000656

AC:

AN:

6101

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000677

AC:

AN:

53150

Other (OTH)

AF:

0.00197

AC:

AN:

1526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000790

Hom.:

Bravo

AF:

0.000604

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000634

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00172

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

not specified

Benign:1

Apr 16, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Uncertain

0.51

D;D;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.69

T;.;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.020

N;N;.

PhyloP100

4.3

PrimateAI

Benign

0.48

PROVEAN

Benign

0.20

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.77

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.041

MVP

0.61

MPC

0.22

ClinPred

0.012

GERP RS

4.0

Varity_R

0.37

gMVP

0.80

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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