X-152868900-C-T

Variant names:

• chrX-152868900-C-T
• rs587784226
• NM_015922.3:c.906C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015922.3(NSDHL):​c.906C>T​(p.Tyr302Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000033 in 1,210,343 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 24)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: NSDHL NM_015922.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=0.297 with no splicing effect.

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.906C>T	p.Tyr302Tyr	synonymous	Exon 8 of 8	NP_057006.1	A0A384NPZ7
	NSDHL	NM_001129765.2		c.906C>T	p.Tyr302Tyr	synonymous	Exon 9 of 9	NP_001123237.1	Q15738
	NSDHL	NM_001441099.1		c.906C>T	p.Tyr302Tyr	synonymous	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.906C>T	p.Tyr302Tyr	synonymous	Exon 8 of 8	ENSP00000359297.3	Q15738
	NSDHL	ENST00000915682.1		c.942C>T	p.Tyr314Tyr	synonymous	Exon 9 of 9	ENSP00000585741.1
	NSDHL	ENST00000440023.5	TSL:5	c.906C>T	p.Tyr302Tyr	synonymous	Exon 9 of 9	ENSP00000391854.1	Q15738

Frequencies

GnomAD3 genomes AF: 0.00000889 AC: 1 AN: 112463 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1097880 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363240

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.0000284 AC: 1 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.00 AC: 0 AN: 54137

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40523

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841800

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome AF: 0.00000889 AC: 1 AN: 112463 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34595

African (AFR) AF: 0.00 AC: 0 AN: 30906

American (AMR) AF: 0.00 AC: 0 AN: 10676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3578

South Asian (SAS) AF: 0.00 AC: 0 AN: 2705

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6224

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53280

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.3
DANN	Benign	0.35
PhyloP100		0.30

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: rs587784226; hg19: chrX-152037444;