chr6-159036489-T-A

Variant names:

• chr6-159036489-T-A
• rs2114782468
• NM_054114.5:c.1534A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_054114.5(TAGAP):​c.1534A>T​(p.Thr512Ser) variant causes a missense change. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T512A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAGAP NM_054114.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.75
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020274132).

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.1534A>T	p.Thr512Ser	missense	Exon 10 of 10	NP_473455.2
	TAGAP	NM_001278733.2		c.1345A>T	p.Thr449Ser	missense	Exon 6 of 6	NP_001265662.1
	TAGAP	NM_152133.3		c.1000A>T	p.Thr334Ser	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.1534A>T	p.Thr512Ser	missense	Exon 10 of 10	ENSP00000356033.4	Q8N103-1
	TAGAP	ENST00000865619.1		c.1534A>T	p.Thr512Ser	missense	Exon 10 of 10	ENSP00000535678.1
	TAGAP	ENST00000642909.1		n.*1193A>T		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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.30
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-3.0	N
PhyloP100		4.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MutPred		0.35		Loss of sheet (P = 0.0315)
MVP		0.043
MPC		0.27
ClinPred		0.17	T
GERP RS		6.1
Varity_R		0.091
gMVP		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2114782468; hg19: chr6-159457521;