chr3-112011840-C-T

Variant summary

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

The NM_001008272.2(TAGLN3):​c.433C>T​(p.Arg145Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

TAGLN3
NM_001008272.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152
Variant links:
Genes affected
TAGLN3 (HGNC:29868): (transgelin 3) Predicted to be involved in central nervous system development. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [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=0.23764747).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAGLN3NM_001008272.2 linkc.433C>T p.Arg145Trp missense_variant Exon 4 of 5 ENST00000478951.6 NP_001008273.1 Q9UI15
TAGLN3NM_001008273.2 linkc.433C>T p.Arg145Trp missense_variant Exon 3 of 4 NP_001008274.1 Q9UI15
TAGLN3NM_013259.3 linkc.433C>T p.Arg145Trp missense_variant Exon 4 of 5 NP_037391.2 Q9UI15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAGLN3ENST00000478951.6 linkc.433C>T p.Arg145Trp missense_variant Exon 4 of 5 1 NM_001008272.2 ENSP00000419105.1 Q9UI15

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152158
Hom.:
0
Cov.:
32
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:
0.000192
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250898
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461642
Hom.:
0
Cov.:
32
AF XY:
0.00000688
AC XY:
5
AN XY:
727124
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:
0.0000464
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000192
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.433C>T (p.R145W) alteration is located in exon 4 (coding exon 3) of the TAGLN3 gene. This alteration results from a C to T substitution at nucleotide position 433, causing the arginine (R) at amino acid position 145 to be replaced by a tryptophan (W). 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
0.16
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.30
T;T;T;T;.
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.96
.;D;.;.;D
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.24
T;T;T;T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Uncertain
2.6
M;M;M;M;.
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.7
D;D;D;D;D
REVEL
Uncertain
0.34
Sift
Benign
0.074
T;T;T;T;D
Sift4G
Uncertain
0.017
D;D;D;D;D
Polyphen
0.98
D;D;D;D;.
Vest4
0.41
MutPred
0.51
Gain of glycosylation at Y144 (P = 0.0048);Gain of glycosylation at Y144 (P = 0.0048);Gain of glycosylation at Y144 (P = 0.0048);Gain of glycosylation at Y144 (P = 0.0048);.;
MVP
0.15
MPC
1.5
ClinPred
0.86
D
GERP RS
1.4
Varity_R
0.17
gMVP
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs200832556; hg19: chr3-111730687; COSMIC: COSV104560462; API