6-159036599-G-A

Position:

• chr6-159036599-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_054114.5(TAGAP):​c.1424C>T​(p.Ala475Val) 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. 15/21 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: 0.451

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045063913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAGAP	NM_054114.5	c.1424C>T	p.Ala475Val	missense_variant	10/10	ENST00000367066.8	NP_473455.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGAP	ENST00000367066.8	c.1424C>T	p.Ala475Val	missense_variant	10/10	1	NM_054114.5	ENSP00000356033.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 14, 2024

The c.1424C>T (p.A475V) alteration is located in exon 10 (coding exon 9) of the TAGAP gene. This alteration results from a C to T substitution at nucleotide position 1424, causing the alanine (A) at amino acid position 475 to be replaced by a valine (V). 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	0.082
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.69	N;N
REVEL	Benign	0.034
Sift	Benign	0.56	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.010	B;.
Vest4		0.033
MutPred		0.25		Loss of glycosylation at P477 (P = 0.1379);.;
MVP		0.043
MPC		0.30
ClinPred		0.063	T
GERP RS		2.9
Varity_R		0.025
gMVP		0.12

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: chr6-159457631;