6-159044945-T-C

Variant names:

• chr6-159044945-T-C
• rs1738074
• NM_054114.5:c.-125A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_054114.5(TAGAP):​c.-125A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 398,082 control chromosomes in the GnomAD database, including 56,700 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19585 hom., cov: 30)
  • Exomes 𝑓: 0.54 (37115 hom.)
• Consequence: TAGAP NM_054114.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.70
• Publications: 131 publications found

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)

ENSG00000288845 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAGAP	NM_054114.5	MANE Select	c.-125A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_473455.2
	TAGAP	NM_054114.5	MANE Select	c.-125A>G		5_prime_UTR	Exon 1 of 10	NP_473455.2
	TAGAP	NM_152133.3		c.-492A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_687034.1	Q8N103-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAGAP	ENST00000367066.8	TSL:1 MANE Select	c.-125A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000356033.4	Q8N103-1
	TAGAP	ENST00000338313.5	TSL:1	c.-125A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000340217.5	Q8N103-4
	TAGAP	ENST00000367066.8	TSL:1 MANE Select	c.-125A>G		5_prime_UTR	Exon 1 of 10	ENSP00000356033.4	Q8N103-1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 74904 AN: 151630 Hom.: 19589 Cov.: 30

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.508

GnomAD4 exome AF: 0.540 AC: 133082 AN: 246332 Hom.: 37115 Cov.: 0 AF XY: 0.543 AC XY: 67846 AN XY: 124852

African (AFR) AF: 0.329 AC: 2364 AN: 7178

American (AMR) AF: 0.399 AC: 2964 AN: 7426

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 5348 AN: 9232

East Asian (EAS) AF: 0.321 AC: 7389 AN: 23018

South Asian (SAS) AF: 0.617 AC: 1873 AN: 3034

European-Finnish (FIN) AF: 0.574 AC: 11955 AN: 20812

Middle Eastern (MID) AF: 0.555 AC: 719 AN: 1296

European-Non Finnish (NFE) AF: 0.582 AC: 91878 AN: 157978

Other (OTH) AF: 0.525 AC: 8592 AN: 16358

GnomAD4 genome AF: 0.494 AC: 74919 AN: 151750 Hom.: 19585 Cov.: 30 AF XY: 0.497 AC XY: 36827 AN XY: 74142

African (AFR) AF: 0.323 AC: 13377 AN: 41364

American (AMR) AF: 0.460 AC: 7011 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2048 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2142 AN: 5152

South Asian (SAS) AF: 0.617 AC: 2965 AN: 4808

European-Finnish (FIN) AF: 0.576 AC: 6034 AN: 10478

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.583 AC: 39582 AN: 67932

Other (OTH) AF: 0.507 AC: 1068 AN: 2108

Alfa AF: 0.546 Hom.: 82881

Bravo AF: 0.470

Asia WGS AF: 0.547 AC: 1901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		2.7
PromoterAI		0.084	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1738074; hg19: chr6-159465977; COSMIC: COSV57850964; COSMIC: COSV57850964;