17-42553172-CG-TC

Variant names:

• chr17-42553172-CG-TC
• NM_000413.4:c.146_147delCGinsTC
• HSD17B1 p.Ala49Val

Variant summary

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

The NM_000413.4(HSD17B1):​c.146_147delCGinsTC​(p.Ala49Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: not found (cov: 34)
• Consequence: HSD17B1 NM_000413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549
• Publications: 0 publications found

Genes affected

HSD17B1 (HGNC:5210): (hydroxysteroid 17-beta dehydrogenase 1) This gene encodes a member of the 17beta-hydroxysteroid dehydrogenase family of short-chain dehydrogenases/reductases. It has a dual function in estrogen activation and androgen inactivation and plays a major role in establishing the estrogen E2 concentration gradient between serum and peripheral tissues. The encoded protein catalyzes the last step in estrogen activation, using NADPH to convert estrogens E1 and E2 and androgens like 4-androstenedione, to testosterone. It has an N-terminal short-chain dehydrogenase domain with a cofactor binding site, and a narrow, hydrophobic C-terminal domain with a steroid substrate binding site. This gene is expressed primarily in the placenta and ovarian granulosa cells, and to a lesser extent, in the endometrium, adipose tissue, and prostate. Polymorphisms in this gene have been linked to breast and prostate cancer. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

HSD17B1-AS1 (HGNC:55314): (HSD17B1 antisense RNA 1)

ENSG00000266929 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000413.4. 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
	HSD17B1	NM_000413.4	MANE Select	c.146_147delCGinsTC	p.Ala49Val	missense	N/A	NP_000404.2	P14061
	HSD17B1	NM_001330219.3		c.146_147delCGinsTC	p.Ala49Val	missense	N/A	NP_001317148.1	A0A0A0MQS7
	HSD17B1	NR_144397.2		n.157_158delCGinsTC		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B1	ENST00000585807.6	TSL:1 MANE Select	c.146_147delCGinsTC	p.Ala49Val	missense	N/A	ENSP00000466799.1	P14061
	HSD17B1	ENST00000225929.5	TSL:2	c.146_147delCGinsTC	p.Ala49Val	missense	N/A	ENSP00000225929.5	A0A0A0MQS7
	HSD17B1	ENST00000587280.1	TSL:2	n.157_158delCGinsTC		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.55

Splicing

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

hg19: chr17-40705190;