rs5969919

chrX-152850288-T-AchrX-152850288-T-CchrX-152850288-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015922.3(NSDHL):c.132T>A(p.Gly44=) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G44G) has been classified as Benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: NSDHL NM_015922.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=-0.673 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSDHL	NM_015922.3	c.132T>A	p.Gly44=	synonymous_variant	3/8	ENST00000370274.8
NSDHL	NM_001129765.2	c.132T>A	p.Gly44=	synonymous_variant	4/9
NSDHL	XM_017029564.2	c.180T>A	p.Gly60=	synonymous_variant	3/8
NSDHL	XM_011531178.3	c.132T>A	p.Gly44=	synonymous_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSDHL	ENST00000370274.8	c.132T>A	p.Gly44=	synonymous_variant	3/8	1	NM_015922.3	P1
NSDHL	ENST00000440023.5	c.132T>A	p.Gly44=	synonymous_variant	4/9	5		P1
NSDHL	ENST00000432467.1	c.132T>A	p.Gly44=	synonymous_variant	4/8	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	4.2
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs5969919; hg19: chrX-152018832;