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NM_177939.3(P4HTM):c.649G>T (p.Gly217Ter) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 5, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003090964.1

Allele description

NM_177939.3(P4HTM):c.649G>T (p.Gly217Ter)

Gene:
P4HTM:prolyl 4-hydroxylase, transmembrane [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.31
Genomic location:
Preferred name:
NM_177939.3(P4HTM):c.649G>T (p.Gly217Ter)
HGVS:
  • NC_000003.12:g.49002521G>T
  • NG_029915.1:g.318G>T
  • NM_177938.2:c.649G>T
  • NM_177939.3:c.649G>TMANE SELECT
  • NP_808807.2:p.Gly217Ter
  • NP_808808.1:p.Gly217Ter
  • NC_000003.11:g.49039954G>T
Protein change:
G217*
Molecular consequence:
  • NM_177938.2:c.649G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_177939.3:c.649G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: CN517202

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003467718Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 5, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Biallelic loss-of-function P4HTM gene variants cause hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities (HIDEA syndrome).

Rahikkala E, Myllykoski M, Hinttala R, Vieira P, Nayebzadeh N, Weiss S, Plomp AS, Bittner RE, Kurki MI, Kuismin O, Lewis AM, Väisänen ML, Kokkonen H, Westermann J, Bernert G, Tuominen H, Palotie A, Aaltonen L, Yang Y, Potocki L, Moilanen J, van Koningsbruggen S, et al.

Genet Med. 2019 Oct;21(10):2355-2363. doi: 10.1038/s41436-019-0503-4. Epub 2019 Apr 3.

PubMed [citation]
PMID:
30940925
PMCID:
PMC6774999

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV003467718.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Gly217*) in the P4HTM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in P4HTM are known to be pathogenic (PMID: 30940925). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with P4HTM-related conditions. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 13, 2023