NM_003244.4(TGIF1):c.451A>G (p.Thr151Ala) AND Holoprosencephaly 4

Germline classification:: Likely benign (2 submissions)
Last evaluated:: Dec 2, 2021
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:: RCV000007396.11

Allele description [Variation Report for NM_003244.4(TGIF1):c.451A>G (p.Thr151Ala)]

NM_003244.4(TGIF1):c.451A>G (p.Thr151Ala)

Gene:

TGIF1:TGFB induced factor homeobox 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.31

Genomic location:

Preferred name:

NM_003244.4(TGIF1):c.451A>G (p.Thr151Ala)

HGVS:

NC_000018.10:g.3457572A>G
NG_007447.2:g.50499A>G
NM_001278682.2:c.460A>G
NM_001278684.2:c.451A>G
NM_001278686.3:c.391A>G
NM_001374396.1:c.391A>G
NM_001374397.1:c.391A>G
NM_003244.4:c.451A>GMANE SELECT
NM_170695.5:c.391A>G
NM_173207.4:c.493A>G
NM_173208.3:c.451A>G
NM_173209.3:c.391A>G
NM_173210.4:c.391A>G
NM_173211.2:c.391A>G
NM_174886.3:c.391A>G
NP_001265611.1:p.Thr154Ala
NP_001265613.1:p.Thr151Ala
NP_001265615.1:p.Thr131Ala
NP_001361325.1:p.Thr131Ala
NP_001361326.1:p.Thr131Ala
NP_003235.1:p.Thr151Ala
NP_733796.3:p.Thr131Ala
NP_775299.1:p.Thr165Ala
NP_775300.1:p.Thr151Ala
NP_775301.1:p.Thr131Ala
NP_775302.1:p.Thr131Ala
NP_775303.1:p.Thr131Ala
NP_777480.1:p.Thr131Ala
NC_000018.9:g.3457570A>G
Q15583:p.Thr280Ala

Protein change:

T131A; THR151ALA

Links:

UniProtKB: Q15583#VAR_009963; OMIM: 602630.0003; dbSNP: rs121909068

NCBI 1000 Genomes Browser:

rs121909068

Molecular consequence:

NM_001278682.2:c.460A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278684.2:c.451A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001278686.3:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374396.1:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001374397.1:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003244.4:c.451A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170695.5:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173207.4:c.493A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173208.3:c.451A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173209.3:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173210.4:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173211.2:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_174886.3:c.391A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Holoprosencephaly 4 (HPE4)
Identifiers:: MONDO: MONDO:0007734; MedGen: C1840528; Orphanet: 2162; OMIM: 142946

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027595	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001606952	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Dec 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000027595

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2000)

germline

literature only

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

SCV001606952

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Dec 2, 2021)

germline

clinical testing

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination.

Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P, Richieri-Costa A, Zackai EH, Massagué J, Muenke M, Elledge SJ.

Nat Genet. 2000 Jun;25(2):205-8.

PubMed [citation]

PMID:: 10835638

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 OMIM, SCV000027595.3

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

Description

In a patient with holoprosencephaly-4 (HPE4; 142946), Gripp et al. (2000) identified an A-to-G transition at nucleotide 451 of the TGIF gene, resulting in a thr151-to-ala substitution. The mutation occurred in a region that encodes a domain that binds SMAD2 (601366) and HDAC (see HDAC1; 601241). The patient had semilobar holoprosencephaly, severe microcephaly, hypotelorism, midface hypoplasia, and a midline cleft. The mother did not carry the mutation and the father was unavailable for analysis. Both the phenotypically normal mother and her affected daughter were heterozygous carriers of a 9-bp deletion in the third exon of the SHH gene (600725.0013).

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001606952.4

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

#	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

Last Updated: Sep 29, 2024

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