6-35478493-G-T

Position:

• chr6-35478493-G-T

Variant summary

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

The NM_003214.4(TEAD3):​c.421C>A​(p.Gln141Lys) 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. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEAD3 NM_003214.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.23

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22693053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEAD3	NM_003214.4	c.421C>A	p.Gln141Lys	missense_variant	6/13	ENST00000338863.13	NP_003205.2
TEAD3	NM_001395214.1	c.421C>A	p.Gln141Lys	missense_variant	6/13		NP_001382143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEAD3	ENST00000338863.13	c.421C>A	p.Gln141Lys	missense_variant	6/13	1	NM_003214.4	ENSP00000345772.8
TEAD3	ENST00000639578.3	c.421C>A	p.Gln141Lys	missense_variant	6/13	1		ENSP00000492431.3
TEAD3	ENST00000402886.9	n.293C>A		non_coding_transcript_exon_variant	4/11	1		ENSP00000384577.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Feb 10, 2023

The c.421C>A (p.Q141K) alteration is located in exon 6 (coding exon 5) of the TEAD3 gene. This alteration results from a C to A substitution at nucleotide position 421, causing the glutamine (Q) at amino acid position 141 to be replaced by a lysine (K). 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	Benign	0.20
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Uncertain	24
DANN	Benign	0.97
Eigen	Benign	-0.066
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	T;.
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.79	N;.
REVEL	Benign	0.070
Sift	Benign	0.32	T;.
Sift4G	Benign	0.34	T;.
MutPred		0.39		Gain of methylation at Q141 (P = 0.0123);Gain of methylation at Q141 (P = 0.0123);
MVP		0.28
ClinPred		0.73	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-35446270;