NM_020800.3(IFT80):c.1093A>G (p.Thr365Ala) AND Jeune thoracic dystrophy

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 19, 2024
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:: RCV000465513.8

Allele description [Variation Report for NM_020800.3(IFT80):c.1093A>G (p.Thr365Ala)]

NM_020800.3(IFT80):c.1093A>G (p.Thr365Ala)

Genes:

TRIM59-IFT80:TRIM59-IFT80 readthrough (NMD candidate) [Gene - HGNC]
IFT80:intraflagellar transport 80 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q25.33

Genomic location:

Preferred name:

NM_020800.3(IFT80):c.1093A>G (p.Thr365Ala)

HGVS:

NC_000003.12:g.160303973T>C
NG_022932.1:g.100560A>G
NM_001190241.2:c.682A>G
NM_001190242.2:c.682A>G
NM_020800.3:c.1093A>GMANE SELECT
NP_001177170.1:p.Thr228Ala
NP_001177171.1:p.Thr228Ala
NP_065851.1:p.Thr365Ala
NC_000003.11:g.160021761T>C
NM_020800.2:c.1093A>G
NR_148401.1:n.1801A>G
NR_148402.1:n.3337A>G
NR_148403.1:n.3604A>G

Protein change:

T228A

Links:

dbSNP: rs140202230

NCBI 1000 Genomes Browser:

rs140202230

Molecular consequence:

NM_001190241.2:c.682A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001190242.2:c.682A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020800.3:c.1093A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_148401.1:n.1801A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148402.1:n.3337A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_148403.1:n.3604A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Jeune thoracic dystrophy (ATD1)
Synonyms:: Jeune syndrome; Infantile thoracic dystrophy; Thoracic pelvic phalangeal dystrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018770; MedGen: C0265275; OMIM: PS208500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000544759	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 19, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29068549, 28492532
SCV000612066	Dan Cohn Lab, University Of California Los Angeles	no assertion criteria provided	Pathogenic (Jun 1, 2017)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV001479582	University of Washington Center for Mendelian Genomics, University of Washington	no assertion criteria provided	Likely pathogenic	inherited	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544759

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 19, 2024)

germline

clinical testing

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

SCV000612066

Dan Cohn Lab, University Of California Los Angeles

no assertion criteria provided

Pathogenic
(Jun 1, 2017)

unknown

research

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

SCV001479582

University of Washington Center for Mendelian Genomics, University of Washington

no assertion criteria provided

Likely pathogenic

inherited

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

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

Expanding the genetic architecture and phenotypic spectrum in the skeletal ciliopathies.

Zhang W, Taylor SP, Ennis HA, Forlenza KN, Duran I, Li B, Sanchez JAO, Nevarez L, Nickerson DA, Bamshad M; University of Washington Center for Mendelian Genomics., Lachman RS, Krakow D, Cohn DH.

Hum Mutat. 2018 Jan;39(1):152-166. doi: 10.1002/humu.23362. Epub 2017 Nov 6.

PubMed [citation]

PMID:: 29068549
PMCID:: PMC6198324

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544759.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 365 of the IFT80 protein (p.Thr365Ala). This variant is present in population databases (rs140202230, gnomAD 0.09%). This missense change has been observed in individual(s) with clinical features of short-rib polydactyly syndrome or asphyxiating thoracic dystrophy (PMID: 29068549; Invitae; external communication). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 406217). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt IFT80 protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Dan Cohn Lab, University Of California Los Angeles, SCV000612066.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From University of Washington Center for Mendelian Genomics, University of Washington, SCV001479582.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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