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NM_000197.2(HSD17B3):c.607-1G>A AND not provided

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jun 9, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001267943.4

Allele description [Variation Report for NM_000197.2(HSD17B3):c.607-1G>A]

NM_000197.2(HSD17B3):c.607-1G>A

Genes:
SLC35D2-HSD17B3:SLC35D2-HSD17B3 readthrough [Gene]
HSD17B3:hydroxysteroid 17-beta dehydrogenase 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.32
Genomic location:
Preferred name:
NM_000197.2(HSD17B3):c.607-1G>A
HGVS:
  • NC_000009.12:g.96244395C>T
  • NG_008157.1:g.62758G>A
  • NM_000197.2:c.607-1G>AMANE SELECT
  • LRG_1296t1:c.607-1G>A
  • LRG_1296:g.62758G>A
  • NC_000009.11:g.99006677C>T
  • NM_000197.1:c.607-1G>A
Note:
NCBI staff reviewed the sequence and mapping information reported in PubMed 8075637 Fig. 3 to determine the location of this allele on the current reference sequence.
Nucleotide change:
IVS8AS, G-A, -1
Links:
OMIM: 605573.0006; dbSNP: rs730880305
NCBI 1000 Genomes Browser:
rs730880305
Molecular consequence:
  • NM_000197.2:c.607-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001446461Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Oct 23, 2020) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004296024Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 9, 2023) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot provided1not providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

Geissler WM, Davis DL, Wu L, Bradshaw KD, Patel S, Mendonca BB, Elliston KO, Wilson JD, Russell DW, Andersson S.

Nat Genet. 1994 May;7(1):34-9.

PubMed [citation]
PMID:
8075637
See all PubMed Citations (7)

Details of each submission

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446461.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004296024.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 4878). Disruption of this splice site has been observed in individual(s) with 17-β-Hydrogenase type 3 deficiency (PMID: 8075637, 28739554). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 8 of the HSD17B3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HSD17B3 are known to be pathogenic (PMID: 23796702, 25740850).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024