Genetic Variant NM_003564.3:c.304C>T (chr1-159919712-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003564.3(TAGLN2):c.304C>T(p.Arg102Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,613,528 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R102H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

TAGLN2
NM_003564.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.211

Publications

2 publications found

Variant links:

Genes affected

TAGLN2 (HGNC:11554): (transgelin 2) The protein encoded by this gene is similar to the protein transgelin, which is one of the earliest markers of differentiated smooth muscle. The specific function of this protein has not yet been determined, although it is thought to be a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

TAGLN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13264802).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003564.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAGLN2	NM_003564.3	MANE Select	c.304C>T	p.Arg102Cys	missense	Exon 3 of 5	NP_003555.1	P37802-1
TAGLN2	NM_001277224.2		c.367C>T	p.Arg123Cys	missense	Exon 3 of 5	NP_001264153.1	P37802-2
TAGLN2	NM_001277223.2		c.304C>T	p.Arg102Cys	missense	Exon 3 of 5	NP_001264152.1	P37802-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAGLN2	ENST00000368097.9	TSL:1 MANE Select	c.304C>T	p.Arg102Cys	missense	Exon 3 of 5	ENSP00000357077.5	P37802-1
TAGLN2	ENST00000368096.5	TSL:1	c.367C>T	p.Arg123Cys	missense	Exon 3 of 5	ENSP00000357076.1	P37802-2
TAGLN2	ENST00000854583.1		c.304C>T	p.Arg102Cys	missense	Exon 3 of 5	ENSP00000524642.1

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000955

AC:

AN:

251302

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

33462

American (AMR)

AF:

0.0000895

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111878

Other (OTH)

AF:

0.0000663

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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

AF:

0.000375

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000240

Hom.:

Bravo

AF:

0.000363

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.72

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.80

M_CAP

Benign

0.041

MetaRNN

Benign

0.13

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.0

PhyloP100

0.21

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.49

Sift

Uncertain

0.029

Sift4G

Uncertain

0.037

Polyphen

0.99

Vest4

0.41

MVP

0.99

MPC

0.52

ClinPred

0.16

GERP RS

4.1

Varity_R

0.18

gMVP

0.57

Mutation Taster

=74/26

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over