Variant rs141571609 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015922.3(NSDHL):c.757C>A(p.Gln253Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,094,317 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

NSDHL
NM_015922.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.53

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2715456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
NSDHL	NM_015922.3 linkuse as main transcript	c.757C>A	p.Gln253Lys	missense_variant	7/8	ENST00000370274.8	NP_057006.1
NSDHL	NM_001129765.2 linkuse as main transcript	c.757C>A	p.Gln253Lys	missense_variant	8/9		NP_001123237.1
NSDHL	XM_017029564.2 linkuse as main transcript	c.805C>A	p.Gln269Lys	missense_variant	7/8		XP_016885053.1
NSDHL	XM_011531178.3 linkuse as main transcript	c.757C>A	p.Gln253Lys	missense_variant	9/10		XP_011529480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
NSDHL	ENST00000370274.8 linkuse as main transcript	c.757C>A	p.Gln253Lys	missense_variant	7/8	1	NM_015922.3	ENSP00000359297	P1
NSDHL	ENST00000440023.5 linkuse as main transcript	c.757C>A	p.Gln253Lys	missense_variant	8/9	5		ENSP00000391854	P1
NSDHL	ENST00000432467.1 linkuse as main transcript	c.757C>A	p.Gln253Lys	missense_variant	8/8	3		ENSP00000396266

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000547

AC:

AN:

182974

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000183

AC:

AN:

1094317

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359769

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000238

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.7

DANN

Benign

0.18

DEOGEN2

Uncertain

0.50

T;T;T

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;.;T

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.2

N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.35

N;N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.19

MVP

0.69

MPC

0.27

ClinPred

0.038

GERP RS

4.5

Varity_R

0.40

gMVP

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over