Genetic Variant TAGAP:p.Pro347Thr (chr6-159036984-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_054114.5(TAGAP):c.1039C>A(p.Pro347Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,613,686 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

TAGAP
NM_054114.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.792

Variant links:

Genes affected

TAGAP (HGNC:15669): (T cell activation RhoGTPase activating protein) This gene encodes a member of the Rho GTPase-activator protein superfamily. The encoded protein may function as a Rho GTPase-activating protein. Alterations in this gene may be associated with several diseases, including rheumatoid arthritis, celiac disease, and multiple sclerosis. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2013]

TAGAP links:

TAGAP-AS1 (HGNC:55239): (TAGAP antisense RNA 1)

TAGAP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041006804).

BP6

Variant 6-159036984-G-T is Benign according to our data. Variant chr6-159036984-G-T is described in ClinVar as [Benign]. Clinvar id is 727285.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGAP	NM_054114.5 link	c.1039C>A	p.Pro347Thr	missense_variant	Exon 10 of 10	ENST00000367066.8	NP_473455.2	Q8N103-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAGAP	ENST00000367066.8 link	c.1039C>A	p.Pro347Thr	missense_variant	Exon 10 of 10	1	NM_054114.5	ENSP00000356033.4		Q8N103-1

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

331

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00768

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000598

AC:

149

AN:

249028

Hom.:

AF XY:

0.000408

AC XY:

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.00803

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000894

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000263

AC:

384

AN:

1461588

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

172

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00878

Gnomad4 AMR exome

AF:

0.000649

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.00219

AC:

333

AN:

152098

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00771

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000421

Hom.:

Bravo

AF:

0.00270

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000708

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.7

DANN

Benign

0.096

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.37

T;T

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

2.0

M;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.94

N;N

REVEL

Benign

0.042

Sift

Benign

0.75

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.024

B;.

Vest4

0.025

MVP

0.043

MPC

0.35

ClinPred

0.0021

GERP RS

1.6

Varity_R

0.028

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over