6-159036070-G-T

Variant names:

• chr6-159036070-G-T
• rs1208108567
• NM_054114.5:c.1953C>A

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.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. 16/22 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
• 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=0.06104693).

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.1953C>A	p.Ser651Arg	missense	Exon 10 of 10	NP_473455.2
	TAGAP	NM_001278733.2		c.1764C>A	p.Ser588Arg	missense	Exon 6 of 6	NP_001265662.1
	TAGAP	NM_152133.3		c.1419C>A	p.Ser473Arg	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.1953C>A	p.Ser651Arg	missense	Exon 10 of 10	ENSP00000356033.4	Q8N103-1
	TAGAP	ENST00000865619.1		c.1953C>A	p.Ser651Arg	missense	Exon 10 of 10	ENSP00000535678.1
	TAGAP	ENST00000642909.1		n.*1612C>A		non_coding_transcript_exon	Exon 9 of 9	ENSP00000495465.1	A0A2R8YEB9

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

African (AFR) AF: 0.0000299 AC: 1 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111148

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.81
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.013
Sift	Benign	0.42	T
Sift4G	Benign	0.55	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
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

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