chr12-3020705-G-T

Variant names:

• chr12-3020705-G-T
• rs367723028
• NM_003213.4:c.655G>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.655G>T​(p.Val219Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,456,988 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TEAD4 NM_003213.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52

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=0.13361451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEAD4	NM_003213.4	c.655G>T	p.Val219Leu	missense_variant	Exon 9 of 13	ENST00000359864.8	NP_003204.2
TEAD4	NM_201441.3	c.526G>T	p.Val176Leu	missense_variant	Exon 8 of 12		NP_958849.1
TEAD4	NM_201443.3	c.268G>T	p.Val90Leu	missense_variant	Exon 7 of 11		NP_958851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEAD4	ENST00000359864.8	c.655G>T	p.Val219Leu	missense_variant	Exon 9 of 13	1	NM_003213.4	ENSP00000352926.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456988 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 724492

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.090
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.034
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.14	T;T;T
Vest4		0.44
MutPred		0.43		.;Loss of catalytic residue at V219 (P = 0.0974);.;
MVP		0.12
ClinPred		0.39	T
GERP RS		3.5
gMVP		0.22

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: rs367723028; hg19: chr12-3129871;