NM_000198.4:c.15C>T

Variant names:

• chr1-119415434-C-T
• rs766474996
• NM_000198.4:c.15C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000198.4(HSD3B2):​c.15C>T​(p.Cys5Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD3B2 NM_000198.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.102
• Publications: 4 publications found

Genes affected

HSD3B2 (HGNC:5218): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2) The protein encoded by this gene is a bifunctional enzyme that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. It plays a crucial role in the biosynthesis of all classes of hormonal steroids. This gene is predominantly expressed in the adrenals and the gonads. Mutations in this gene are associated with 3-beta-hydroxysteroid dehydrogenase, type II, deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

HSD3B2 Gene-Disease associations (from GenCC):

• congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000307032 (HGNC:):

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=-0.36).
• BP6: Variant 1-119415434-C-T is Benign according to our data. Variant chr1-119415434-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2836295.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.102 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000198.4. 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
	HSD3B2	NM_000198.4	MANE Select	c.15C>T	p.Cys5Cys	synonymous	Exon 2 of 4	NP_000189.1	P26439-1
	HSD3B2	NM_001166120.2		c.15C>T	p.Cys5Cys	synonymous	Exon 2 of 4	NP_001159592.1	P26439-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B2	ENST00000369416.4	TSL:1 MANE Select	c.15C>T	p.Cys5Cys	synonymous	Exon 2 of 4	ENSP00000358424.3	P26439-1
	HSD3B2	ENST00000543831.5	TSL:3	c.15C>T	p.Cys5Cys	synonymous	Exon 2 of 4	ENSP00000445122.1	P26439-1
	HSD3B2	ENST00000902254.1		c.15C>T	p.Cys5Cys	synonymous	Exon 1 of 3	ENSP00000572313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.10
PromoterAI		0.069	Neutral
Mutation Taster		=100/0	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: rs766474996; hg19: chr1-119958057;