rs745539655

Variant names:

• chr18-36797020-A-C
• rs745539655
• NM_015476.4:c.688T>G

Your query was ambiguous. Multiple possible variants found:

• chr18-36797020-A-C
• chr18-36797020-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015476.4(TPGS2):​c.688T>G​(p.Tyr230Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y230H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPGS2 NM_015476.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.63
• Publications: 0 publications found

Genes affected

TPGS2 (HGNC:24561): (tubulin polyglutamylase complex subunit 2) This gene encodes a protein that is a component of the neuronal polyglutamylase complex, which plays a role in post-translational addition of glutamate residues to C-terminal tubulin tails. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPGS2	NM_015476.4	c.688T>G	p.Tyr230Asp	missense_variant	Exon 7 of 7	ENST00000334295.9	NP_056291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPGS2	ENST00000334295.9	c.688T>G	p.Tyr230Asp	missense_variant	Exon 7 of 7	1	NM_015476.4	ENSP00000335144.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;.;.;.
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.5	M;.;.;.
PhyloP100		5.6
PROVEAN	Uncertain	-2.7	D;.;D;.
REVEL	Benign	0.24
Sift	Uncertain	0.018	D;.;D;.
Sift4G	Uncertain	0.0090	D;D;D;.
Polyphen		0.91	P;.;D;.
Vest4		0.60
MutPred		0.47		Loss of sheet (P = 0.0063);.;.;.;
MVP		0.54
MPC		0.26
ClinPred		0.94	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
Mutation Taster		=82/18	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: rs745539655; hg19: chr18-34376983;