chr6-35481549-C-T

Variant names:

• chr6-35481549-C-T
• rs9394299
• NM_003214.4:c.268-1175G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003214.4(TEAD3):​c.268-1175G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 152,178 control chromosomes in the GnomAD database, including 10,815 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 0.29 (10815 hom., cov: 32)
• Consequence: TEAD3 NM_003214.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEAD3	NM_003214.4	c.268-1175G>A		intron_variant	Intron 3 of 12	ENST00000338863.13	NP_003205.2
TEAD3	NM_001395214.1	c.268-1427G>A		intron_variant	Intron 3 of 12		NP_001382143.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEAD3	ENST00000338863.13	c.268-1175G>A		intron_variant	Intron 3 of 12	1	NM_003214.4	ENSP00000345772.8
TEAD3	ENST00000639578.3	c.268-1427G>A		intron_variant	Intron 3 of 12	1		ENSP00000492431.3
TEAD3	ENST00000402886.9	n.203-2233G>A		intron_variant	Intron 2 of 10	1		ENSP00000384577.5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43648 AN: 152060 Hom.: 10758 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.288 AC: 43758 AN: 152178 Hom.: 10815 Cov.: 32 AF XY: 0.287 AC XY: 21348 AN XY: 74412

African (AFR) AF: 0.669 AC: 27758 AN: 41490

American (AMR) AF: 0.218 AC: 3329 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1364 AN: 5180

South Asian (SAS) AF: 0.277 AC: 1337 AN: 4822

European-Finnish (FIN) AF: 0.0861 AC: 912 AN: 10594

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7197 AN: 68018

Other (OTH) AF: 0.294 AC: 621 AN: 2112

Alfa AF: 0.147 Hom.: 3108

Bravo AF: 0.316

Asia WGS AF: 0.365 AC: 1267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0060
DANN	Benign	0.54
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9394299; hg19: chr6-35449326;