rs1336191687

Variant names:

• chr17-42553268-C-G
• NM_000413.4:c.242C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-42553268-C-G
• chr17-42553268-C-T

Variant summary

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

The NM_000413.4(HSD17B1):​c.242C>G​(p.Thr81Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 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. T81I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HSD17B1 NM_000413.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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

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
HSD17B1	NM_000413.4	c.242C>G	p.Thr81Ser	missense_variant	Exon 2 of 6	ENST00000585807.6	NP_000404.2
HSD17B1	NM_001330219.3	c.242C>G	p.Thr81Ser	missense_variant	Exon 2 of 6		NP_001317148.1
HSD17B1	NR_144397.2	n.253C>G		non_coding_transcript_exon_variant	Exon 2 of 5
HSD17B1-AS1	NR_144402.1	n.1535G>C		non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B1	ENST00000585807.6	c.242C>G	p.Thr81Ser	missense_variant	Exon 2 of 6	1	NM_000413.4	ENSP00000466799.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458046 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 725538

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.58
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.53	T;T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.72	N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.90	.;N
REVEL	Benign	0.11
Sift	Benign	0.63	.;T
Sift4G	Benign	0.72	T;T
Polyphen		0.0	B;.
Vest4		0.15
MutPred		0.30		Gain of disorder (P = 0.0354);Gain of disorder (P = 0.0354);
MVP		0.87
MPC		0.28
ClinPred		0.13	T
GERP RS		2.2
Varity_R		0.14
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.86		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.86		Position offset: -5

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: chr17-40705286;