NM_025193.4:c.45_46delAG
Variant summary
Our verdict is Pathogenic. The variant received 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_025193.4(HSD3B7):c.45_46delAG(p.Gly17LeufsTer26) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000746 in 1,608,782 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Consequence
NM_025193.4 frameshift
Scores
Clinical Significance
Conservation
Publications
- congenital bile acid synthesis defect 1Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Pathogenic. The variant received 14 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152270Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000372 AC: 9AN: 242084 AF XY: 0.0000380 show subpopulations
GnomAD4 exome AF: 0.0000810 AC: 118AN: 1456512Hom.: 0 AF XY: 0.0000911 AC XY: 66AN XY: 724454 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74390 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Congenital bile acid synthesis defect 1 Pathogenic:5
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The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.004%). Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000002885 /PMID: 12679481, 28776642 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. -
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PVS1+PM2_Supporting+PM3_Strong+PP4 -
not provided Pathogenic:2
HSD3B7: PVS1, PM2, PM3 -
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HSD3B7-related disorder Pathogenic:1
The HSD3B7 c.45_46delAG variant is predicted to result in a frameshift and premature protein termination (p.Gly17Leufs*26). This variant was reported in individuals with 3 beta-hydroxysteroid oxidoreductase deficiency or congenital bile acid synthesis defect (for example, see Cheng et al. 2003. PubMed ID: 12679481, reported as 63, ΔAG; Stalke et al. 2018. PubMed ID: 28776642). This variant is reported in 0.013% of alleles in individuals of African descent in gnomAD. Frameshift variants in HSD3B7 are expected to be pathogenic. This variant is interpreted as pathogenic. -
Congenital bile acid synthesis defect Pathogenic:1
PVS1(strong),PM2, PM3 moderate -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at