chr6-159036840-G-C

Variant names:

• chr6-159036840-G-C
• NM_054114.5:c.1183C>G

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.1183C>G​(p.Gln395Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TAGAP NM_054114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• 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=0.15861028).

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.1183C>G	p.Gln395Glu	missense	Exon 10 of 10	NP_473455.2
	TAGAP	NM_001278733.2		c.994C>G	p.Gln332Glu	missense	Exon 6 of 6	NP_001265662.1
	TAGAP	NM_152133.3		c.649C>G	p.Gln217Glu	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.1183C>G	p.Gln395Glu	missense	Exon 10 of 10	ENSP00000356033.4	Q8N103-1
	TAGAP	ENST00000865619.1		c.1183C>G	p.Gln395Glu	missense	Exon 10 of 10	ENSP00000535678.1
	TAGAP	ENST00000642909.1		n.*842C>G		non_coding_transcript_exon	Exon 9 of 9	ENSP00000495465.1	A0A2R8YEB9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.071
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.14
Sift	Benign	0.16	T
Sift4G	Benign	0.099	T
Polyphen		0.43	B
Vest4		0.14
MutPred		0.15		Gain of phosphorylation at S400 (P = 0.1492)
MVP		0.27
MPC		0.60
ClinPred		0.54	D
GERP RS		5.8
Varity_R		0.13
gMVP		0.19
Mutation Taster		=90/10	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

hg19: chr6-159457872;