Genetic Variant TAGLN3:p.Pro46Thr (chr3-111999558-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001008272.2(TAGLN3):c.136C>A(p.Pro46Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P46S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TAGLN3
NM_001008272.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

0 publications found

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]

TAGLN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.101741314).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAGLN3	NM_001008272.2	MANE Select	c.136C>A	p.Pro46Thr	missense	Exon 2 of 5	NP_001008273.1	Q9UI15
TAGLN3	NM_001008273.2		c.136C>A	p.Pro46Thr	missense	Exon 1 of 4	NP_001008274.1	Q9UI15
TAGLN3	NM_013259.3		c.136C>A	p.Pro46Thr	missense	Exon 2 of 5	NP_037391.2	Q9UI15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAGLN3	ENST00000478951.6	TSL:1 MANE Select	c.136C>A	p.Pro46Thr	missense	Exon 2 of 5	ENSP00000419105.1	Q9UI15
TAGLN3	ENST00000273368.8	TSL:1	c.136C>A	p.Pro46Thr	missense	Exon 2 of 5	ENSP00000273368.4	Q9UI15
TAGLN3	ENST00000455401.6	TSL:1	c.136C>A	p.Pro46Thr	missense	Exon 1 of 4	ENSP00000391160.2	Q9UI15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251042

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111918

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.33

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.59

M_CAP

Benign

0.042

MetaRNN

Benign

0.10

MetaSVM

Uncertain

-0.082

MutationAssessor

Benign

1.7

PhyloP100

1.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.38

REVEL

Benign

0.22

Sift

Benign

0.45

Sift4G

Benign

0.41

Polyphen

0.0020

Vest4

0.27

MutPred

0.33

Loss of glycosylation at P47 (P = 0.0472)

MVP

0.42

MPC

0.90

ClinPred

0.13

GERP RS

2.6

PromoterAI

0.038

Neutral

(source)

Varity_R

0.048

gMVP

0.62

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over