TGFA p.Gln21His

Variant names:

• chr2-70514890-C-A
• NM_003236.4:c.63G>T
• TGFA p.Gln21His

Your query was ambiguous. Multiple possible variants found:

• chr2-70514890-C-A
• chr2-70514890-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003236.4(TGFA):​c.63G>T​(p.Gln21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q21Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGFA NM_003236.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23354232).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003236.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	NM_003236.4	MANE Select	c.63G>T	p.Gln21His	missense	Exon 2 of 6	NP_003227.1	P01135-1
	TGFA	NM_001308158.2		c.81G>T	p.Gln27His	missense	Exon 2 of 6	NP_001295087.1	F8VNR3
	TGFA	NM_001308159.2		c.81G>T	p.Gln27His	missense	Exon 2 of 6	NP_001295088.1	E7EPT6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGFA	ENST00000295400.11	TSL:1 MANE Select	c.63G>T	p.Gln21His	missense	Exon 2 of 6	ENSP00000295400.6	P01135-1
	TGFA	ENST00000444975.5	TSL:1	c.81G>T	p.Gln27His	missense	Exon 2 of 6	ENSP00000404131.1	F8VNR3
	TGFA	ENST00000450929.5	TSL:1	c.81G>T	p.Gln27His	missense	Exon 2 of 6	ENSP00000414127.1	E7EPT6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.1
DANN	Benign	0.96
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.21
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.59	T
Varity_R		0.061
gMVP		0.52
Mutation Taster		=77/23	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-70742022; COSMIC: COSV54912991;