rs554966762

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003236.4(TGFA):​c.416G>C​(p.Arg139Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R139Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

TGFA
NM_003236.4 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFANM_003236.4 linkc.416G>C p.Arg139Pro missense_variant Exon 5 of 6 ENST00000295400.11 NP_003227.1 P01135-1
TGFANM_001308158.2 linkc.434G>C p.Arg145Pro missense_variant Exon 5 of 6 NP_001295087.1 P01135F8VNR3
TGFANM_001308159.2 linkc.431G>C p.Arg144Pro missense_variant Exon 5 of 6 NP_001295088.1 P01135E7EPT6
TGFANM_001099691.3 linkc.413G>C p.Arg138Pro missense_variant Exon 5 of 6 NP_001093161.1 P01135-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFAENST00000295400.11 linkc.416G>C p.Arg139Pro missense_variant Exon 5 of 6 1 NM_003236.4 ENSP00000295400.6 P01135-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251306
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461756
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.57
D;.;.;.;.
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.86
D;D;D;D;D
M_CAP
Benign
0.0054
T
MetaRNN
Uncertain
0.62
D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.;.;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.2
D;D;D;D;D
REVEL
Benign
0.15
Sift
Benign
0.060
T;D;D;D;D
Sift4G
Benign
0.17
T;T;T;T;T
Polyphen
0.92
P;D;P;D;D
Vest4
0.67
MutPred
0.44
.;.;.;.;Gain of loop (P = 0.0045);
MVP
0.25
MPC
0.59
ClinPred
0.94
D
GERP RS
5.0
Varity_R
0.49
gMVP
0.65

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: rs554966762; hg19: chr2-70680409; API