2-70453253-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003236.4(TGFA):c.440T>A(p.Leu147Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
TGFA
NM_003236.4 missense
NM_003236.4 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 4.50
Genes affected
TGFA (HGNC:11765): (transforming growth factor alpha) This gene encodes a growth factor that is a ligand for the epidermal growth factor receptor, which activates a signaling pathway for cell proliferation, differentiation and development. This protein may act as either a transmembrane-bound ligand or a soluble ligand. This gene has been associated with many types of cancers, and it may also be involved in some cases of cleft lip/palate. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TGFA | NM_003236.4 | c.440T>A | p.Leu147Gln | missense_variant | 5/6 | ENST00000295400.11 | NP_003227.1 | |
TGFA | NM_001308158.2 | c.458T>A | p.Leu153Gln | missense_variant | 5/6 | NP_001295087.1 | ||
TGFA | NM_001308159.2 | c.455T>A | p.Leu152Gln | missense_variant | 5/6 | NP_001295088.1 | ||
TGFA | NM_001099691.3 | c.437T>A | p.Leu146Gln | missense_variant | 5/6 | NP_001093161.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TGFA | ENST00000295400.11 | c.440T>A | p.Leu147Gln | missense_variant | 5/6 | 1 | NM_003236.4 | ENSP00000295400 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32
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GnomAD4 exome Cov.: 30
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74320
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2022 | The c.440T>A (p.L147Q) alteration is located in exon 5 (coding exon 5) of the TGFA gene. This alteration results from a T to A substitution at nucleotide position 440, causing the leucine (L) at amino acid position 147 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;T;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;D;D
Vest4
MutPred
0.48
.;.;.;.;Gain of catalytic residue at L153 (P = 0.0179);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at