chr16-30987821-A-C

Variant names:

• chr16-30987821-A-C
• rs9938550
• NM_025193.4:c.748A>C

Variant summary

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

The NM_025193.4(HSD3B7):​c.748A>C​(p.Thr250Pro) variant causes a missense 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. 15/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T250A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: HSD3B7 NM_025193.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 59 publications found

Genes affected

HSD3B7 (HGNC:18324): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 7) This gene encodes an enzyme which is involved in the initial stages of the synthesis of bile acids from cholesterol and a member of the short-chain dehydrogenase/reductase superfamily. The encoded protein is a membrane-associated endoplasmic reticulum protein which is active against 7-alpha hydrosylated sterol substrates. Mutations in this gene are associated with a congenital bile acid synthesis defect which leads to neonatal cholestasis, a form of progressive liver disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

HSD3B7 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

ENSG00000279196 (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=0.086544305).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025193.4. 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
	HSD3B7	NM_025193.4	MANE Select	c.748A>C	p.Thr250Pro	missense	Exon 7 of 7	NP_079469.2
	HSD3B7	NM_001142777.2		c.585A>C	p.Gln195His	missense	Exon 6 of 6	NP_001136249.1	Q9H2F3-2
	HSD3B7	NM_001142778.2		c.585A>C	p.Gln195His	missense	Exon 6 of 6	NP_001136250.1	Q9H2F3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B7	ENST00000297679.10	TSL:1 MANE Select	c.748A>C	p.Thr250Pro	missense	Exon 7 of 7	ENSP00000297679.5	Q9H2F3-1
	HSD3B7	ENST00000867909.1		c.871A>C	p.Thr291Pro	missense	Exon 7 of 7	ENSP00000537968.1
	HSD3B7	ENST00000867910.1		c.871A>C	p.Thr291Pro	missense	Exon 7 of 7	ENSP00000537969.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 61

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
PhyloP100		-0.60
Varity_R		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9938550; hg19: chr16-30999142;