dbSNP rs199700477: TGFA:p.Ala38Val (chr2-70465718-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_003236.4(TGFA):c.113C>T(p.Ala38Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A38E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TGFA
NM_003236.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.17

Publications

0 publications found

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]

TGFA Gene-Disease associations (from GenCC):

tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TGFA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3386935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGFA	NM_003236.4 link	c.113C>T	p.Ala38Val	missense_variant	Exon 3 of 6	ENST00000295400.11	NP_003227.1	P01135-1
TGFA	NM_001308158.2 link	c.131C>T	p.Ala44Val	missense_variant	Exon 3 of 6		NP_001295087.1	P01135F8VNR3
TGFA	NM_001308159.2 link	c.128C>T	p.Ala43Val	missense_variant	Exon 3 of 6		NP_001295088.1	P01135E7EPT6
TGFA	NM_001099691.3 link	c.110C>T	p.Ala37Val	missense_variant	Exon 3 of 6		NP_001093161.1	P01135-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGFA	ENST00000295400.11 link	c.113C>T	p.Ala38Val	missense_variant	Exon 3 of 6	1	NM_003236.4	ENSP00000295400.6		P01135-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111980

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;.;.;.;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D;D

M_CAP

Benign

0.035

MetaRNN

Benign

0.34

T;T;T;T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.6

M;.;.;.;.;.

PhyloP100

7.2

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.5

N;D;D;D;N;D

REVEL

Benign

0.20

Sift

Uncertain

0.013

D;D;D;D;D;D

Sift4G

Uncertain

0.013

D;D;D;D;D;.

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.57

MutPred

0.34

.;.;.;.;Loss of disorder (P = 0.086);.;

MVP

0.22

MPC

0.79

ClinPred

0.98

GERP RS

5.0

PromoterAI

0.0070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.32

gMVP

0.69

Mutation Taster

=16/84

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs199700477

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over