6-159036333-G-T

Variant names:

• chr6-159036333-G-T
• rs1475855292
• NM_054114.5:c.1690C>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.1690C>A​(p.Gln564Lys) 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. 14/21 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: 2.95

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=0.15099517).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGAP	NM_054114.5	c.1690C>A	p.Gln564Lys	missense_variant	Exon 10 of 10	ENST00000367066.8	NP_473455.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAGAP	ENST00000367066.8	c.1690C>A	p.Gln564Lys	missense_variant	Exon 10 of 10	1	NM_054114.5	ENSP00000356033.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1690C>A (p.Q564K) alteration is located in exon 10 (coding exon 9) of the TAGAP gene. This alteration results from a C to A substitution at nucleotide position 1690, causing the glutamine (Q) at amino acid position 564 to be replaced by a lysine (K). 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.14
Sift	Benign	0.19	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.15	B;.
Vest4		0.11
MutPred		0.55		Gain of ubiquitination at Q564 (P = 0.0155);.;
MVP		0.12
MPC		0.55
ClinPred		0.14	T
GERP RS		4.6
Varity_R		0.083
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs1475855292; hg19: chr6-159457365;