rs376794048
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_015922.3(NSDHL):c.1020C>T(p.Cys340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000148 in 1,210,073 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 59 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000080 ( 0 hom., 3 hem., cov: 24)
Exomes 𝑓: 0.00015 ( 0 hom. 56 hem. )
Consequence
NSDHL
NM_015922.3 synonymous
NM_015922.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.07
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant X-152869014-C-T is Benign according to our data. Variant chrX-152869014-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 436068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-152869014-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.07 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000802 (9/112153) while in subpopulation NFE AF= 0.00015 (8/53170). AF 95% confidence interval is 0.0000745. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 3 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSDHL | NM_015922.3 | c.1020C>T | p.Cys340= | synonymous_variant | 8/8 | ENST00000370274.8 | |
NSDHL | NM_001129765.2 | c.1020C>T | p.Cys340= | synonymous_variant | 9/9 | ||
NSDHL | XM_017029564.2 | c.1068C>T | p.Cys356= | synonymous_variant | 8/8 | ||
NSDHL | XM_011531178.3 | c.1020C>T | p.Cys340= | synonymous_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSDHL | ENST00000370274.8 | c.1020C>T | p.Cys340= | synonymous_variant | 8/8 | 1 | NM_015922.3 | P1 | |
NSDHL | ENST00000440023.5 | c.1020C>T | p.Cys340= | synonymous_variant | 9/9 | 5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000802 AC: 9AN: 112153Hom.: 0 Cov.: 24 AF XY: 0.0000874 AC XY: 3AN XY: 34339
GnomAD3 genomes
?
AF:
AC:
9
AN:
112153
Hom.:
Cov.:
24
AF XY:
AC XY:
3
AN XY:
34339
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000115 AC: 21AN: 183129Hom.: 0 AF XY: 0.0000887 AC XY: 6AN XY: 67641
GnomAD3 exomes
AF:
AC:
21
AN:
183129
Hom.:
AF XY:
AC XY:
6
AN XY:
67641
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000155 AC: 170AN: 1097920Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 56AN XY: 363292
GnomAD4 exome
AF:
AC:
170
AN:
1097920
Hom.:
Cov.:
31
AF XY:
AC XY:
56
AN XY:
363292
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000802 AC: 9AN: 112153Hom.: 0 Cov.: 24 AF XY: 0.0000874 AC XY: 3AN XY: 34339
GnomAD4 genome
?
AF:
AC:
9
AN:
112153
Hom.:
Cov.:
24
AF XY:
AC XY:
3
AN XY:
34339
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 16, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at