NM_003213.4:c.337A>G

Variant names:

• chr12-3012215-A-G
• NM_003213.4:c.337A>G

Variant summary

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

The NM_003213.4(TEAD4):​c.337A>G​(p.Ile113Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEAD4 NM_003213.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

Genes affected

TEAD4 (HGNC:11717): (TEA domain transcription factor 4) This gene product is a member of the transcriptional enhancer factor (TEF) family of transcription factors, which contain the TEA/ATTS DNA-binding domain. It is preferentially expressed in the skeletal muscle, and binds to the M-CAT regulatory element found in promoters of muscle-specific genes to direct their gene expression. Alternatively spliced transcripts encoding distinct isoforms, some of which are translated through the use of a non-AUG (UUG) initiation codon, have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003213.4. 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
	TEAD4	NM_003213.4	MANE Select	c.337A>G	p.Ile113Val	missense	Exon 5 of 13	NP_003204.2
	TEAD4	NM_201441.3		c.337A>G	p.Ile113Val	missense	Exon 5 of 12	NP_958849.1	Q15561-3
	TEAD4	NM_201443.3		c.-51A>G		5_prime_UTR	Exon 3 of 11	NP_958851.1	Q15561-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEAD4	ENST00000359864.8	TSL:1 MANE Select	c.337A>G	p.Ile113Val	missense	Exon 5 of 13	ENSP00000352926.3	Q15561-1
	TEAD4	ENST00000358409.7	TSL:1	c.337A>G	p.Ile113Val	missense	Exon 5 of 12	ENSP00000351184.3	Q15561-3
	TEAD4	ENST00000397122.6	TSL:1	c.-51A>G		5_prime_UTR	Exon 3 of 11	ENSP00000380311.2	Q15561-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.79	T
PhyloP100		4.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.18
Sift	Benign	0.21	T
Sift4G	Benign	0.10	T
MutPred		0.54		Loss of catalytic residue at I113 (P = 0.2786)
MVP		0.39
ClinPred		0.96	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.44
Mutation Taster		=247/53	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

Other links and lift over

hg19: chr12-3121381;