X-152846398-T-C

Position:

• chrX-152846398-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015922.3(NSDHL):​c.74T>C​(p.Val25Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: NSDHL NM_015922.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.774

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11091474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NSDHL	NM_015922.3	c.74T>C	p.Val25Ala	missense_variant	2/8	ENST00000370274.8	NP_057006.1
NSDHL	NM_001129765.2	c.74T>C	p.Val25Ala	missense_variant	3/9		NP_001123237.1
NSDHL	XM_017029564.2	c.122T>C	p.Val41Ala	missense_variant	2/8		XP_016885053.1
NSDHL	XM_011531178.3	c.74T>C	p.Val25Ala	missense_variant	4/10		XP_011529480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSDHL	ENST00000370274.8	c.74T>C	p.Val25Ala	missense_variant	2/8	1	NM_015922.3	ENSP00000359297.3
NSDHL	ENST00000440023.5	c.74T>C	p.Val25Ala	missense_variant	3/9	5		ENSP00000391854.1
NSDHL	ENST00000432467.1	c.74T>C	p.Val25Ala	missense_variant	3/8	3		ENSP00000396266.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Child syndrome;C3151781:CK syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.0
DANN	Benign	0.40
DEOGEN2	Benign	0.26	T;T;T
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.27	T;.;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.19
Sift	Benign	0.47	T;T;T
Sift4G	Benign	0.80	T;T;T
Polyphen		0.0050	B;B;.
Vest4		0.18
MutPred		0.27		Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);Loss of loop (P = 0.0203);
MVP		0.33
MPC		0.26
ClinPred		0.049	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152014942; COSMIC: COSV64744255;