Variant 19-7916533-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001195259.2(TGFBR3L):c.266T>C(p.Val89Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000466 in 1,501,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

TGFBR3L
NM_001195259.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

Variant links:

Genes affected

TGFBR3L (HGNC:44152): (transforming growth factor beta receptor 3 like) Predicted to enable glycosaminoglycan binding activity; transforming growth factor beta-activated receptor activity; and type II transforming growth factor beta receptor binding activity. Predicted to contribute to transforming growth factor beta binding activity. Predicted to be involved in several processes, including blood vessel morphogenesis; regulation of transforming growth factor beta receptor signaling pathway; and transforming growth factor beta receptor signaling pathway. Predicted to be integral component of membrane. Predicted to be active in cell surface and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

TGFBR3L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TGFBR3L	NM_001195259.2 linkuse as main transcript	c.266T>C	p.Val89Ala	missense_variant	1/6	ENST00000565886.2	NP_001182188.1
TGFBR3L	XM_011527610.3 linkuse as main transcript	c.266T>C	p.Val89Ala	missense_variant	1/4		XP_011525912.1
TGFBR3L	XM_011527613.3 linkuse as main transcript	c.266T>C	p.Val89Ala	missense_variant	1/5		XP_011525915.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGFBR3L	ENST00000565886.2 linkuse as main transcript	c.266T>C	p.Val89Ala	missense_variant	1/6	5	NM_001195259.2	ENSP00000457962	P1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000967

AC:

AN:

103380

Hom.:

AF XY:

0.0000178

AC XY:

AN XY:

56024

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000445

AC:

AN:

1349246

Hom.:

Cov.:

AF XY:

0.00000605

AC XY:

AN XY:

661500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000566

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152010

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Aug 13, 2021

The c.266T>C (p.V89A) alteration is located in exon 1 (coding exon 1) of the TGFBR3L gene. This alteration results from a T to C substitution at nucleotide position 266, causing the valine (V) at amino acid position 89 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

Pathogenic

0.90

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.41

M_CAP

Pathogenic

0.93

MetaRNN

Uncertain

0.73

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-2.9

Sift

Uncertain

0.0020

Sift4G

Benign

1.0

Vest4

0.53

MVP

0.76

GERP RS

3.6

Varity_R

0.36

gMVP

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over