rs769596311

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195259.2(TGFBR3L):​c.229C>A​(p.Arg77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000461 in 1,519,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R77G) has been classified 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

2
1
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.113
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15867093).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFBR3LNM_001195259.2 linkc.229C>A p.Arg77Ser missense_variant Exon 1 of 6 ENST00000565886.2 NP_001182188.1 H3BV60-2
TGFBR3LNM_001419781.1 linkc.157C>A p.Arg53Ser missense_variant Exon 2 of 7 NP_001406710.1
TGFBR3LXM_011527610.3 linkc.229C>A p.Arg77Ser missense_variant Exon 1 of 4 XP_011525912.1
TGFBR3LXM_011527613.3 linkc.229C>A p.Arg77Ser missense_variant Exon 1 of 5 XP_011525915.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFBR3LENST00000565886.2 linkc.229C>A p.Arg77Ser missense_variant Exon 1 of 6 5 NM_001195259.2 H3BV60-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152124
Hom.:
0
Cov.:
33
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:
0.0000163
AC:
2
AN:
123066
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67456
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:
0.0000436
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000439
AC:
6
AN:
1367782
Hom.:
0
Cov.:
31
AF XY:
0.00000595
AC XY:
4
AN XY:
672250
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:
0.00000562
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152124
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74314
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
Alfa
AF:
0.0000435
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000581
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.43
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
23
DANN
Benign
0.95
DEOGEN2
Benign
0.12
T
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.54
T
M_CAP
Pathogenic
0.65
D
MetaRNN
Benign
0.16
T
MutationAssessor
Benign
0.20
N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.11
N
Sift
Benign
0.95
T
Sift4G
Benign
0.72
T
Vest4
0.19
MVP
0.77
GERP RS
2.6
Varity_R
0.13
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs769596311; hg19: chr19-7981381; API