NM_000862.3:c.279C>A

Variant names:

• chr1-119511636-C-A
• rs587715330
• NM_000862.3:c.279C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000862.3(HSD3B1):​c.279C>A​(p.His93Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 2 publications found

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

ENSG00000293080 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11345285).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000862.3. 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
	HSD3B1	NM_000862.3	MANE Select	c.279C>A	p.His93Gln	missense	Exon 3 of 4	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.279C>A	p.His93Gln	missense	Exon 3 of 4	NP_001315544.1	P14060

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B1	ENST00000369413.8	TSL:1 MANE Select	c.279C>A	p.His93Gln	missense	Exon 3 of 4	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.279C>A	p.His93Gln	missense	Exon 2 of 3	ENSP00000432268.1	P14060
	HSD3B1	ENST00000492140.1	TSL:2	n.414C>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151538 Hom.: 0 Cov.: 31

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: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250964 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151656 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74178

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41026

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2108

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.032
DANN	Benign	0.41
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.065	N
PhyloP100		-0.47
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.61	N
REVEL	Benign	0.059
Sift	Benign	0.35	T
Sift4G	Benign	0.59	T
Polyphen		0.036	B
Vest4		0.10
MVP		0.86
MPC		0.027
ClinPred		0.048	T
GERP RS		-0.65
Varity_R		0.048
gMVP		0.35
Mutation Taster		=89/11	polymorphism

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: rs587715330; hg19: chr1-120054259;