rs144110486

Variant names:

• chrX-152868895-T-A
• rs144110486
• NM_015922.3:c.901T>A

Your query was ambiguous. Multiple possible variants found:

• chrX-152868895-T-A
• chrX-152868895-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015922.3(NSDHL):​c.901T>A​(p.Tyr301Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y301H) has been classified 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: 7.89
• Publications: 1 publications found

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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• CK syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.907

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015922.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSDHL	NM_015922.3	MANE Select	c.901T>A	p.Tyr301Asn	missense	Exon 8 of 8	NP_057006.1	A0A384NPZ7
	NSDHL	NM_001129765.2		c.901T>A	p.Tyr301Asn	missense	Exon 9 of 9	NP_001123237.1	Q15738
	NSDHL	NM_001441099.1		c.901T>A	p.Tyr301Asn	missense	Exon 10 of 10	NP_001428028.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSDHL	ENST00000370274.8	TSL:1 MANE Select	c.901T>A	p.Tyr301Asn	missense	Exon 8 of 8	ENSP00000359297.3	Q15738
	NSDHL	ENST00000915682.1		c.937T>A	p.Tyr313Asn	missense	Exon 9 of 9	ENSP00000585741.1
	NSDHL	ENST00000440023.5	TSL:5	c.901T>A	p.Tyr301Asn	missense	Exon 9 of 9	ENSP00000391854.1	Q15738

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.9
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.87
Sift	Uncertain	0.023	D
Sift4G	Benign	0.078	T
Polyphen		1.0	D
Vest4		0.93
MutPred		0.56		Gain of sheet (P = 0.0477)
MVP		0.92
MPC		1.0
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.77
gMVP		0.92
Mutation Taster		=48/52	disease causing

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

Other links and lift over

dbSNP: rs144110486; hg19: chrX-152037439;