Variant 18-36797020-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015476.4(TPGS2):c.688T>C(p.Tyr230His) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,445,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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

TPGS2
NM_015476.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

Variant links:

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 links:

TPGS2 (HGNC:):

TPGS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32989252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPGS2	NM_015476.4 linkuse as main transcript	c.688T>C	p.Tyr230His	missense_variant	7/7	ENST00000334295.9	NP_056291.2	Q68CL5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPGS2	ENST00000334295.9 linkuse as main transcript	c.688T>C	p.Tyr230His	missense_variant	7/7	1	NM_015476.4	ENSP00000335144.3		Q68CL5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000428

AC:

AN:

233866

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000582

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1445330

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 05, 2024

The c.688T>C (p.Y230H) alteration is located in exon 7 (coding exon 7) of the TPGS2 gene. This alteration results from a T to C substitution at nucleotide position 688, causing the tyrosine (Y) at amino acid position 230 to be replaced by a histidine (H). 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

0.31

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0094

T;.;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.5

M;.;.;.

PROVEAN

Benign

-1.5

N;.;N;.

REVEL

Benign

0.12

Sift

Benign

0.044

D;.;D;.

Sift4G

Uncertain

0.017

D;D;D;.

Polyphen

0.99

D;.;D;.

Vest4

0.32

MutPred

0.42

Loss of sheet (P = 0.0181);.;.;.;

MVP

0.54

MPC

0.074

ClinPred

0.52

GERP RS

4.6

Varity_R

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over