2-70453221-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000295400.11(TGFA):ā€‹c.472A>Cā€‹(p.Thr158Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)

Consequence

TGFA
ENST00000295400.11 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37351665).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TGFANM_003236.4 linkuse as main transcriptc.472A>C p.Thr158Pro missense_variant 5/6 ENST00000295400.11 NP_003227.1
TGFANM_001308158.2 linkuse as main transcriptc.490A>C p.Thr164Pro missense_variant 5/6 NP_001295087.1
TGFANM_001308159.2 linkuse as main transcriptc.487A>C p.Thr163Pro missense_variant 5/6 NP_001295088.1
TGFANM_001099691.3 linkuse as main transcriptc.469A>C p.Thr157Pro missense_variant 5/6 NP_001093161.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TGFAENST00000295400.11 linkuse as main transcriptc.472A>C p.Thr158Pro missense_variant 5/61 NM_003236.4 ENSP00000295400 P4P01135-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152198
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsApr 13, 2022The c.472A>C (p.T158P) alteration is located in exon 5 (coding exon 5) of the TGFA gene. This alteration results from a A to C substitution at nucleotide position 472, causing the threonine (T) at amino acid position 158 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.20
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.56
D;.;.;.;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.63
T;T;T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.37
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-2.8
D;D;D;D;D
REVEL
Benign
0.14
Sift
Uncertain
0.0030
D;D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.44
MutPred
0.17
.;.;.;.;Gain of relative solvent accessibility (P = 0.0522);
MVP
0.23
MPC
0.74
ClinPred
0.98
D
GERP RS
5.9
Varity_R
0.55
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1181697045; hg19: chr2-70680353; API