chr18-36797001-G-C

Position:

• chr18-36797001-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015476.4(TPGS2):​c.707C>G​(p.Thr236Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPGS2 NM_015476.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.68

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]

TPGS2 (HGNC:):

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=0.15626556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPGS2	NM_015476.4	c.707C>G	p.Thr236Arg	missense_variant	7/7	ENST00000334295.9	NP_056291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPGS2	ENST00000334295.9	c.707C>G	p.Thr236Arg	missense_variant	7/7	1	NM_015476.4	ENSP00000335144.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Sep 11, 2024

The c.707C>G (p.T236R) alteration is located in exon 7 (coding exon 7) of the TPGS2 gene. This alteration results from a C to G substitution at nucleotide position 707, causing the threonine (T) at amino acid position 236 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.0062	T;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.;.
PROVEAN	Benign	-0.90	N;.;N;.
REVEL	Benign	0.027
Sift	Benign	0.47	T;.;T;.
Sift4G	Benign	0.48	T;T;T;.
Polyphen		0.48	P;.;B;.
Vest4		0.12
MutPred		0.18		Gain of helix (P = 0.027);.;.;.;
MVP		0.40
MPC		0.067
ClinPred		0.25	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr18-34376964;