Variant 2-105267484-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004257.6(TGFBRAP1):c.2482C>G(p.Pro828Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TGFBRAP1
NM_004257.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.24

Variant links:

Genes affected

TGFBRAP1 (HGNC:16836): (transforming growth factor beta receptor associated protein 1) This gene encodes a protein that binds to transforming growth factor-beta (TGF-beta) receptors and plays a role in TGF-beta signaling. The encoded protein acts as a chaprone in signaling downstream of TGF-beta. It is involved in signal-dependent association with SMAD4. The protein is also a component of mammalian CORVET, a multisubunit tethering protein complex that is involved in fusion of early endosomes. [provided by RefSeq, Jun 2016]

TGFBRAP1 links:

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ACMG classification

Classification made for transcript

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, 0.768

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGFBRAP1	NM_004257.6 link	c.2482C>G	p.Pro828Ala	missense_variant	12/12	ENST00000393359.7	NP_004248.2	Q8WUH2
TGFBRAP1	NM_001142621.3 link	c.2482C>G	p.Pro828Ala	missense_variant	12/12		NP_001136093.1	Q8WUH2
TGFBRAP1	NM_001426428.1 link	c.2482C>G	p.Pro828Ala	missense_variant	12/13		NP_001413357.1
TGFBRAP1	NM_001328646.3 link	c.2406+1788C>G		intron_variant			NP_001315575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBRAP1	ENST00000393359.7 link	c.2482C>G	p.Pro828Ala	missense_variant	12/12	1	NM_004257.6	ENSP00000377027.2		Q8WUH2
TGFBRAP1	ENST00000595531.5 link	c.2482C>G	p.Pro828Ala	missense_variant	11/11	1		ENSP00000471434.2		Q8WUH2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2024

The c.2482C>G (p.P828A) alteration is located in exon 12 (coding exon 11) of the TGFBRAP1 gene. This alteration results from a C to G substitution at nucleotide position 2482, causing the proline (P) at amino acid position 828 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;.;.

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.4

M;M;M

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.3

.;N;N

REVEL

Benign

0.19

Sift

Benign

0.19

.;T;T

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.59

P;P;P

Vest4

0.63

MutPred

0.69

Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);Loss of loop (P = 0.2237);

MVP

0.64

MPC

0.95

ClinPred

0.97

GERP RS

5.5

Varity_R

0.099

gMVP

0.42

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over