14-75958704-TA-T

Position:

• chr14-75958704-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003239.5(TGFB3):​c.*482del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 173,256 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (7 hom., cov: 31)
  • Exomes 𝑓: 0.32 (0 hom.)
• Consequence: TGFB3 NM_003239.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.68

Genes affected

TGFB3 (HGNC:11769): (transforming growth factor beta 3) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate a latency-associated peptide (LAP) and a mature peptide, and is found in either a latent form composed of a mature peptide homodimer, a LAP homodimer, and a latent TGF-beta binding protein, or in an active form consisting solely of the mature peptide homodimer. The mature peptide may also form heterodimers with other TGF-beta family members. This protein is involved in embryogenesis and cell differentiation, and may play a role in wound healing. Mutations in this gene are a cause of aortic aneurysms and dissections, as well as familial arrhythmogenic right ventricular dysplasia 1. [provided by RefSeq, Aug 2016]

IFT43 (HGNC:29669): (intraflagellar transport 43) This gene encodes a subunit of the intraflagellar transport complex A (IFT-A). IFT-A is a multiprotein complex that plays an important role in cilia assembly and maintenance by mediating retrograde ciliary transport. Mutations in this gene are a cause of cranioectodermal dysplasia-3 (CED3), also known as Sensenbrenner syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-75958704-TA-T is Benign according to our data. Variant chr14-75958704-TA-T is described in ClinVar as [Benign]. Clinvar id is 1269859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFB3	NM_003239.5	c.*482del		3_prime_UTR_variant	7/7	ENST00000238682.8	NP_003230.1
TGFB3	NM_001329939.2	c.*482del		3_prime_UTR_variant	8/8		NP_001316868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFB3	ENST00000238682.8	c.*482del		3_prime_UTR_variant	7/7	1	NM_003239.5	ENSP00000238682	P1
TGFB3	ENST00000556674.2	c.*482del		3_prime_UTR_variant	8/8	3		ENSP00000502685	P1
TGFB3	ENST00000554980.5	n.2102del		non_coding_transcript_exon_variant	4/4	2
IFT43	ENST00000555677.5	n.90-30165del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1820 AN: 140204 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00796

Gnomad ASJ AF: 0.00730

Gnomad EAS AF: 0.00509

Gnomad SAS AF: 0.00257

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.00762

Gnomad OTH AF: 0.0126

GnomAD4 exome AF: 0.317 AC: 10470 AN: 33036 Hom.: 0 Cov.: 0 AF XY: 0.315 AC XY: 5322 AN XY: 16904

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.303

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.0131 AC: 1837 AN: 140220 Hom.: 7 Cov.: 31 AF XY: 0.0143 AC XY: 971 AN XY: 67952

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.00796

Gnomad4 ASJ AF: 0.00730

Gnomad4 EAS AF: 0.00571

Gnomad4 SAS AF: 0.00258

Gnomad4 FIN AF: 0.0378

Gnomad4 NFE AF: 0.00762

Gnomad4 OTH AF: 0.0125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs199646113; hg19: chr14-76425047;