rs2076173

Positions:

• chr6-35474620-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003214.4(TEAD3):​c.*424T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 176,370 control chromosomes in the GnomAD database, including 14,742 homozygotes. 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: 𝑓 0.33 (14346 hom., cov: 32)
  • Exomes 𝑓: 0.14 (396 hom.)
• Consequence: TEAD3 NM_003214.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEAD3	NM_003214.4	c.*424T>C		3_prime_UTR_variant	13/13	ENST00000338863.13	NP_003205.2
TEAD3	NM_001395214.1	c.*424T>C		3_prime_UTR_variant	13/13		NP_001382143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEAD3	ENST00000338863.13	c.*424T>C		3_prime_UTR_variant	13/13	1	NM_003214.4	ENSP00000345772	P5
TEAD3	ENST00000402886.9	c.*1133T>C		3_prime_UTR_variant, NMD_transcript_variant	11/11	1		ENSP00000384577	A2

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49849 AN: 152014 Hom.: 14286 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.145 AC: 3506 AN: 24238 Hom.: 396 Cov.: 0 AF XY: 0.154 AC XY: 1962 AN XY: 12760

Gnomad4 AFR exome AF: 0.733

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.0621

Gnomad4 NFE exome AF: 0.0935

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.328 AC: 49961 AN: 152132 Hom.: 14346 Cov.: 32 AF XY: 0.327 AC XY: 24298 AN XY: 74362

Gnomad4 AFR AF: 0.769

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.347

Alfa AF: 0.163 Hom.: 5393

Bravo AF: 0.363

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs2076173; hg19: chr6-35442397; COSMIC: COSV58818860; COSMIC: COSV58818860;