NM_015922.3:c.132T>G

Variant names:

• chrX-152850288-T-G
• rs5969919
• NM_015922.3:c.132T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_015922.3(NSDHL):​c.132T>G​(p.Gly44Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (27281 hom., 27862 hem., cov: 23)
  • Exomes 𝑓: 0.87 (279620 hom. 318527 hem.)
  • Failed GnomAD Quality Control
• Consequence: NSDHL NM_015922.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.673
• Publications: 21 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant X-152850288-T-G is Benign according to our data. Variant chrX-152850288-T-G is described in ClinVar as Benign. ClinVar VariationId is 159450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.673 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.132T>G	p.Gly44Gly	synonymous	Exon 3 of 8	NP_057006.1	A0A384NPZ7
	NSDHL	NM_001129765.2		c.132T>G	p.Gly44Gly	synonymous	Exon 4 of 9	NP_001123237.1	Q15738
	NSDHL	NM_001441099.1		c.132T>G	p.Gly44Gly	synonymous	Exon 5 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.132T>G	p.Gly44Gly	synonymous	Exon 3 of 8	ENSP00000359297.3	Q15738
	NSDHL	ENST00000915682.1		c.168T>G	p.Gly56Gly	synonymous	Exon 4 of 9	ENSP00000585741.1
	NSDHL	ENST00000440023.5	TSL:5	c.132T>G	p.Gly44Gly	synonymous	Exon 4 of 9	ENSP00000391854.1	Q15738

Frequencies

GnomAD3 genomes AF: 0.838 AC: 92769 AN: 110674 Hom.: 27288 Cov.: 23

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.960

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.915

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.856

GnomAD2 exomes AF: 0.882 AC: 161742 AN: 183420 AF XY: 0.886

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.940

Gnomad ASJ exome AF: 0.918

Gnomad EAS exome AF: 0.916

Gnomad FIN exome AF: 0.852

Gnomad NFE exome AF: 0.867

Gnomad OTH exome AF: 0.880

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.874 AC: 959053 AN: 1097942 Hom.: 279620 Cov.: 48 AF XY: 0.877 AC XY: 318527 AN XY: 363394

African (AFR) AF: 0.744 AC: 19636 AN: 26397

American (AMR) AF: 0.937 AC: 32992 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 17745 AN: 19386

East Asian (EAS) AF: 0.945 AC: 28536 AN: 30205

South Asian (SAS) AF: 0.939 AC: 50809 AN: 54136

European-Finnish (FIN) AF: 0.847 AC: 34307 AN: 40527

Middle Eastern (MID) AF: 0.923 AC: 3804 AN: 4123

European-Non Finnish (NFE) AF: 0.868 AC: 731056 AN: 841890

Other (OTH) AF: 0.872 AC: 40168 AN: 46076

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.838 AC: 92823 AN: 110730 Hom.: 27281 Cov.: 23 AF XY: 0.846 AC XY: 27862 AN XY: 32952

African (AFR) AF: 0.740 AC: 22527 AN: 30431

American (AMR) AF: 0.909 AC: 9442 AN: 10389

Ashkenazi Jewish (ASJ) AF: 0.920 AC: 2431 AN: 2643

East Asian (EAS) AF: 0.915 AC: 3203 AN: 3502

South Asian (SAS) AF: 0.929 AC: 2398 AN: 2581

European-Finnish (FIN) AF: 0.841 AC: 4949 AN: 5886

Middle Eastern (MID) AF: 0.862 AC: 188 AN: 218

European-Non Finnish (NFE) AF: 0.865 AC: 45738 AN: 52890

Other (OTH) AF: 0.857 AC: 1298 AN: 1514

Alfa AF: 0.865 Hom.: 17218

Bravo AF: 0.841

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Child syndrome (1)
-	-	1	CK syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		-0.67
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs5969919; hg19: chrX-152018832; COSMIC: COSV64743481;