rs746594673

Variant names:

• chr12-3018558-C-G
• rs746594673
• NM_003213.4:c.497C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-3018558-C-G
• chr12-3018558-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003213.4(TEAD4):​c.497C>G​(p.Ala166Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEAD4 NM_003213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.96

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23412791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEAD4	NM_003213.4	c.497C>G	p.Ala166Gly	missense_variant	Exon 7 of 13	ENST00000359864.8	NP_003204.2
TEAD4	NM_201441.3	c.368C>G	p.Ala123Gly	missense_variant	Exon 6 of 12		NP_958849.1
TEAD4	NM_201443.3	c.110C>G	p.Ala37Gly	missense_variant	Exon 5 of 11		NP_958851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEAD4	ENST00000359864.8	c.497C>G	p.Ala166Gly	missense_variant	Exon 7 of 13	1	NM_003213.4	ENSP00000352926.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Benign	0.81
DEOGEN2	Benign	0.072	T;T;.;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-0.60	T
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.030	N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.74	T;T;T;T
Sift4G	Benign	0.60	T;T;T;T
Vest4		0.43
MutPred		0.48		.;Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);.;
MVP		0.30
ClinPred		0.81	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.17

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

Other links and lift over

dbSNP: rs746594673; hg19: chr12-3127724;