6-159035967-G-A

Variant names:

• chr6-159035967-G-A
• rs1425584735
• NM_054114.5:c.2056C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_054114.5(TAGAP):​c.2056C>T​(p.Pro686Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: TAGAP NM_054114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.324
• Publications: 0 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08731192).

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.2056C>T	p.Pro686Ser	missense	Exon 10 of 10	NP_473455.2
	TAGAP	NM_001278733.2		c.1867C>T	p.Pro623Ser	missense	Exon 6 of 6	NP_001265662.1
	TAGAP	NM_152133.3		c.1522C>T	p.Pro508Ser	missense	Exon 9 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.2056C>T	p.Pro686Ser	missense	Exon 10 of 10	ENSP00000356033.4	Q8N103-1
	TAGAP	ENST00000865619.1		c.2056C>T	p.Pro686Ser	missense	Exon 10 of 10	ENSP00000535678.1
	TAGAP	ENST00000642909.1		n.*1715C>T		non_coding_transcript_exon	Exon 9 of 9	ENSP00000495465.1	A0A2R8YEB9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251344 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727228

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.32
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.018
Sift	Benign	0.15	T
Sift4G	Benign	0.48	T
Polyphen		0.14	B
Vest4		0.26
MutPred		0.15		Gain of catalytic residue at P686 (P = 0.0155)
MVP		0.043
MPC		0.55
ClinPred		0.057	T
GERP RS		-1.9
Varity_R		0.026
gMVP		0.20
Mutation Taster		=97/3	polymorphism

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: rs1425584735; hg19: chr6-159456999;