chr6-35475583-C-T

Position:

• chr6-35475583-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003214.4(TEAD3):​c.1024G>A​(p.Val342Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEAD3 NM_003214.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

Genes affected

TEAD3 (HGNC:11716): (TEA domain transcription factor 3) 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 predominantly expressed in the placenta and is involved in the transactivation of the chorionic somatomammotropin-B gene enhancer. Translation of this protein is initiated at a non-AUG (AUA) start codon. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEAD3	NM_003214.4	c.1024G>A	p.Val342Met	missense_variant	11/13	ENST00000338863.13	NP_003205.2
TEAD3	NM_001395214.1	c.1024G>A	p.Val342Met	missense_variant	11/13		NP_001382143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEAD3	ENST00000338863.13	c.1024G>A	p.Val342Met	missense_variant	11/13	1	NM_003214.4	ENSP00000345772.8
TEAD3	ENST00000639578.3	c.1024G>A	p.Val342Met	missense_variant	11/13	1		ENSP00000492431.3
TEAD3	ENST00000402886.9	n.*425G>A		non_coding_transcript_exon_variant	9/11	1		ENSP00000384577.5
TEAD3	ENST00000402886.9	n.*425G>A		3_prime_UTR_variant	9/11	1		ENSP00000384577.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.1024G>A (p.V342M) alteration is located in exon 11 (coding exon 10) of the TEAD3 gene. This alteration results from a G to A substitution at nucleotide position 1024, causing the valine (V) at amino acid position 342 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;.
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-0.50	T
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.9	D;.
REVEL	Uncertain	0.48
Sift	Benign	0.071	T;.
Sift4G	Uncertain	0.054	T;.
MutPred		0.74		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.48
ClinPred		0.99	D
GERP RS		4.7
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-35443360;