6-159040754-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_054114.5(TAGAP):c.556G>T(p.Asp186Tyr) 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. 12/21 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: 0.654

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17540395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAGAP	NM_054114.5	c.556G>T	p.Asp186Tyr	missense_variant	7/10	ENST00000367066.8
TAGAP-AS1	NR_183546.1	n.701-165C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAGAP	ENST00000367066.8	c.556G>T	p.Asp186Tyr	missense_variant	7/10	1	NM_054114.5	P1
TAGAP-AS1	ENST00000646912.1	n.26-1044C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2022

The c.556G>T (p.D186Y) alteration is located in exon 7 (coding exon 6) of the TAGAP gene. This alteration results from a G to T substitution at nucleotide position 556, causing the aspartic acid (D) at amino acid position 186 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	15
Dann	Uncertain	0.98
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.67	T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M;.;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.060
Sift	Uncertain	0.019	D;D;D
Sift4G	Uncertain	0.046	D;D;D
Polyphen		0.82	P;.;B
Vest4		0.31
MutPred		0.58		Loss of disorder (P = 0.0166);.;Loss of disorder (P = 0.0166);
MVP		0.082
MPC		0.76
ClinPred		0.56	D
GERP RS		-0.63
Varity_R		0.12
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-159461786;