Genetic Variant NM_054114.5:c.1031G>A (chr6-159036992-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_054114.5(TAGAP):c.1031G>A(p.Ser344Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,613,784 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 7 hom. )

Consequence

TAGAP
NM_054114.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0640

Publications

8 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025393069).

BP6

Variant 6-159036992-C-T is Benign according to our data. Variant chr6-159036992-C-T is described in ClinVar as Benign. ClinVar VariationId is 735880.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00546 (831/152236) while in subpopulation AFR AF = 0.0193 (802/41548). AF 95% confidence interval is 0.0182. There are 4 homozygotes in GnomAd4. There are 375 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_054114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAGAP	NM_054114.5	MANE Select	c.1031G>A	p.Ser344Asn	missense	Exon 10 of 10	NP_473455.2
TAGAP	NM_001278733.2		c.842G>A	p.Ser281Asn	missense	Exon 6 of 6	NP_001265662.1
TAGAP	NM_152133.3		c.497G>A	p.Ser166Asn	missense	Exon 9 of 9	NP_687034.1	Q8N103-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TAGAP	ENST00000367066.8	TSL:1 MANE Select	c.1031G>A	p.Ser344Asn	missense	Exon 10 of 10	ENSP00000356033.4	Q8N103-1
TAGAP	ENST00000865619.1		c.1031G>A	p.Ser344Asn	missense	Exon 10 of 10	ENSP00000535678.1
TAGAP	ENST00000642909.1		n.*690G>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000495465.1	A0A2R8YEB9

Frequencies

GnomAD3 genomes

AF:

0.00546

AC:

831

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00148

AC:

367

AN:

248532

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.0206

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000233

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000608

AC:

889

AN:

1461548

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

410

AN XY:

727082

show subpopulations

African (AFR)

AF:

0.0193

AC:

645

AN:

33476

American (AMR)

AF:

0.000559

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53260

Middle Eastern (MID)

AF:

0.00746

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000103

AC:

114

AN:

1111916

Other (OTH)

AF:

0.000994

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

113

169

226

282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00546

AC:

831

AN:

152236

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0193

AC:

802

AN:

41548

American (AMR)

AF:

0.000785

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68020

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

122

162

203

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00216

Hom.:

Bravo

AF:

0.00637

ESP6500AA

AF:

0.0200

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00189

AC:

230

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.25

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.029

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.064

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.28

REVEL

Benign

0.026

Sift

Benign

0.38

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.018

MVP

0.082

MPC

0.28

ClinPred

0.0050

GERP RS

-4.5

Varity_R

0.026

gMVP

0.14

Mutation Taster

=100/0

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

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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