Variant X-152846451-C-T 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.108+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,020,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000018 ( 0 hom. 5 hem. )

Consequence

NSDHL
NM_015922.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.45

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=-0.92).

BP6

Variant X-152846451-C-T is Benign according to our data. Variant chrX-152846451-C-T is described in ClinVar as [Benign]. Clinvar id is 2195806.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000178 (2/112306) while in subpopulation AMR AF= 0.000188 (2/10656). AF 95% confidence interval is 0.0000329. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.

BS2

High Hemizygotes in GnomAdExome at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
NSDHL	NM_015922.3 linkuse as main transcript	c.108+19C>T	intron_variant	ENST00000370274.8
NSDHL	NM_001129765.2 linkuse as main transcript	c.108+19C>T	intron_variant
NSDHL	XM_011531178.3 linkuse as main transcript	c.108+19C>T	intron_variant
NSDHL	XM_017029564.2 linkuse as main transcript	c.156+19C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
NSDHL	ENST00000370274.8 linkuse as main transcript	c.108+19C>T	intron_variant	1	NM_015922.3	P1
NSDHL	ENST00000432467.1 linkuse as main transcript	c.108+19C>T	intron_variant	3
NSDHL	ENST00000440023.5 linkuse as main transcript	c.108+19C>T	intron_variant	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34486

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

182455

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

66999

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.0000176

AC:

AN:

907700

Hom.:

Cov.:

AF XY:

0.0000205

AC XY:

AN XY:

243812

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000200

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000105

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112306

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34486

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000188

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 12, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

Cadd

Benign

0.70

Dann

Benign

0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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