chr3-112011775-C-A

Variant summary

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

The NM_001008272.2(TAGLN3):​c.368C>A​(p.Ala123Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,650 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: 6.9e-7 ( 0 hom. )

Consequence

TAGLN3
NM_001008272.2 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.752

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAGLN3NM_001008272.2 linkc.368C>A p.Ala123Glu missense_variant Exon 4 of 5 ENST00000478951.6 NP_001008273.1 Q9UI15
TAGLN3NM_001008273.2 linkc.368C>A p.Ala123Glu missense_variant Exon 3 of 4 NP_001008274.1 Q9UI15
TAGLN3NM_013259.3 linkc.368C>A p.Ala123Glu 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.368C>A p.Ala123Glu missense_variant Exon 4 of 5 1 NM_001008272.2 ENSP00000419105.1 Q9UI15

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459650
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726182
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.368C>A (p.A123E) alteration is located in exon 4 (coding exon 3) of the TAGLN3 gene. This alteration results from a C to A substitution at nucleotide position 368, causing the alanine (A) at amino acid position 123 to be replaced by a glutamic acid (E). 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
0.98
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.74
D;D;D;D;.
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
.;D;.;.;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.75
D;D;D;D;D
MetaSVM
Uncertain
0.0019
D
MutationAssessor
Uncertain
2.6
M;M;M;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Uncertain
-3.3
D;D;D;D;D
REVEL
Uncertain
0.41
Sift
Uncertain
0.011
D;D;D;D;T
Sift4G
Benign
0.081
T;T;T;T;T
Polyphen
0.95
P;P;P;P;.
Vest4
0.80
MutPred
0.49
Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);Gain of disorder (P = 0.0876);.;
MVP
0.49
MPC
2.0
ClinPred
0.97
D
GERP RS
6.0
Varity_R
0.64
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

hg19: chr3-111730622; API