6-159036070-G-T

Variant names:

• chr6-159036070-G-T
• rs1208108567
• NM_054114.5:c.1953C>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.1953C>A​(p.Ser651Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TAGAP NM_054114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.805

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=0.06104693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGAP	NM_054114.5	c.1953C>A	p.Ser651Arg	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.1953C>A	p.Ser651Arg	missense_variant	Exon 10 of 10	1	NM_054114.5	ENSP00000356033.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460772 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726442

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1953C>A (p.S651R) 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 1953, causing the serine (S) at amino acid position 651 to be replaced by an arginine (R). 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	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.046
DANN	Benign	0.86
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.061	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.013
Sift	Benign	0.42	T;T
Sift4G	Benign	0.55	T;T
Polyphen		0.0060	B;.
Vest4		0.12
MutPred		0.13		Loss of phosphorylation at S651 (P = 0.0129);.;
MVP		0.068
MPC		0.41
ClinPred		0.13	T
GERP RS		-8.0
Varity_R		0.044
gMVP		0.23

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: rs1208108567; hg19: chr6-159457102; COSMIC: COSV100487652; COSMIC: COSV100487652;