chr19-7916623-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195259.2(TGFBR3L):​c.278C>T​(p.Ala93Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000831 in 1,419,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

TGFBR3L
NM_001195259.2 missense, splice_region

Scores

2
2
10
Splicing: ADA: 0.0002068
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.455
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022650301).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TGFBR3LNM_001195259.2 linkc.278C>T p.Ala93Val missense_variant, splice_region_variant Exon 2 of 6 ENST00000565886.2 NP_001182188.1 H3BV60-2
TGFBR3LXM_011527610.3 linkc.356C>T p.Ala119Val missense_variant Exon 1 of 4 XP_011525912.1
TGFBR3LXM_011527613.3 linkc.356C>T p.Ala119Val missense_variant Exon 1 of 5 XP_011525915.1
TGFBR3LNM_001419781.1 linkc.206C>T p.Ala69Val missense_variant, splice_region_variant Exon 3 of 7 NP_001406710.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TGFBR3LENST00000565886.2 linkc.278C>T p.Ala93Val missense_variant, splice_region_variant Exon 2 of 6 5 NM_001195259.2 H3BV60-2

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00375
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000200
AC:
7
AN:
34932
Hom.:
0
AF XY:
0.000274
AC XY:
5
AN XY:
18272
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00612
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000239
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000701
Gnomad OTH exome
AF:
0.000772
GnomAD4 exome
AF:
0.0000813
AC:
103
AN:
1267680
Hom.:
0
Cov.:
31
AF XY:
0.000101
AC XY:
62
AN XY:
616098
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00256
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000231
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.000228
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152118
Hom.:
0
Cov.:
33
AF XY:
0.000162
AC XY:
12
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.000156
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.278C>T (p.A93V) alteration is located in exon 2 (coding exon 2) of the TGFBR3L gene. This alteration results from a C to T substitution at nucleotide position 278, causing the alanine (A) at amino acid position 93 to be replaced by a valine (V). 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
0.22
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
20
DANN
Uncertain
0.97
DEOGEN2
Benign
0.12
T
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.60
T
M_CAP
Pathogenic
0.69
D
MetaRNN
Benign
0.023
T
MutationAssessor
Benign
0.035
N
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
0.17
N
Sift
Benign
1.0
T
Sift4G
Uncertain
0.040
D
Vest4
0.29
MVP
0.71
GERP RS
2.9
Varity_R
0.056
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00021
dbscSNV1_RF
Benign
0.0080
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.

Other links and lift over

dbSNP: rs772132754; hg19: chr19-7981508; API