6-159036986-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_054114.5(TAGAP):c.1037G>A(p.Gly346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,613,620 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0091 (21 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (27 hom.)
• Consequence: TAGAP NM_054114.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.144

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

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029199123).
• BP6: Variant 6-159036986-C-T is Benign according to our data. Variant chr6-159036986-C-T is described in ClinVar as [Benign]. Clinvar id is 776179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00908 (1382/152166) while in subpopulation AFR AF= 0.0316 (1311/41492). AF 95% confidence interval is 0.0302. There are 21 homozygotes in gnomad4. There are 657 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAGAP	NM_054114.5	c.1037G>A	p.Gly346Asp	missense_variant	10/10	ENST00000367066.8
TAGAP-AS1	NR_183546.1	n.701-3933C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAGAP	ENST00000367066.8	c.1037G>A	p.Gly346Asp	missense_variant	10/10	1	NM_054114.5	P1
TAGAP-AS1	ENST00000646912.1	n.26-4812C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00908 AC: 1381 AN: 152050 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00817

GnomAD3 exomes AF: 0.00260 AC: 646 AN: 248666 Hom.: 8 AF XY: 0.00207 AC XY: 279 AN XY: 134700

Gnomad AFR exome AF: 0.0354

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00111 AC: 1629 AN: 1461454 Hom.: 27 Cov.: 31 AF XY: 0.000975 AC XY: 709 AN XY: 727040

Gnomad4 AFR exome AF: 0.0384

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000782

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.00908 AC: 1382 AN: 152166 Hom.: 21 Cov.: 32 AF XY: 0.00883 AC XY: 657 AN XY: 74394

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00808

Alfa AF: 0.00159 Hom.: 4

Bravo AF: 0.0102

ESP6500AA AF: 0.0302 AC: 133

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00315 AC: 382

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.20
Dann	Benign	0.44
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.32	T;T
MetaRNN	Benign	0.0029	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.0090
Sift	Benign	0.21	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0020	B;.
Vest4		0.041
MVP		0.043
MPC		0.38
ClinPred		0.0049	T
GERP RS		-1.6
Varity_R		0.042
gMVP		0.21

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

Other links and lift over

dbSNP: rs35263580; hg19: chr6-159458018;