rs778944174

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000413.4(HSD17B1):​c.38C>A​(p.Ser13*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

HSD17B1
NM_000413.4 stop_gained

Scores

2
4
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.96
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HSD17B1NM_000413.4 linkc.38C>A p.Ser13* stop_gained Exon 1 of 6 ENST00000585807.6 NP_000404.2 P14061
HSD17B1NM_001330219.3 linkc.38C>A p.Ser13* stop_gained Exon 1 of 6 NP_001317148.1 A0A0A0MQS7
HSD17B1NR_144397.2 linkn.49C>A non_coding_transcript_exon_variant Exon 1 of 5
HSD17B1-AS1NR_144402.1 linkn.1832G>T non_coding_transcript_exon_variant Exon 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HSD17B1ENST00000585807.6 linkc.38C>A p.Ser13* stop_gained Exon 1 of 6 1 NM_000413.4 ENSP00000466799.1 P14061

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.60
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
42
DANN
Uncertain
0.99
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.94
D
Vest4
0.70
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.56
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.56
Position offset: 2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40704989; API