1-119507538-G-T

Variant names:

• chr1-119507538-G-T
• rs145698516
• NM_000862.3:c.62G>T

Variant summary

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

The NM_000862.3(HSD3B1):​c.62G>T​(p.Arg21Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,694 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.62G>T	p.Arg21Leu	missense	Exon 2 of 4	NP_000853.1	P14060
	HSD3B1	NM_001328615.1		c.62G>T	p.Arg21Leu	missense	Exon 2 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.62G>T	p.Arg21Leu	missense	Exon 2 of 4	ENSP00000358421.3	P14060
	HSD3B1	ENST00000528909.1	TSL:1	c.62G>T	p.Arg21Leu	missense	Exon 1 of 3	ENSP00000432268.1	P14060
	HSD3B1	ENST00000531340.5	TSL:3	c.62G>T	p.Arg21Leu	missense	Exon 2 of 3	ENSP00000435999.1	E9PRN7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461694 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111874

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	0.50
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.065	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.32
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.034	D
Polyphen		0.52	P
Vest4		0.47
MVP		0.75
MPC		0.12
ClinPred		0.94	D
GERP RS		-1.6
PromoterAI		-0.035	Neutral
Varity_R		0.25
gMVP		0.23
Mutation Taster		=84/16	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: rs145698516; hg19: chr1-120050161;