Variant 18-36786937-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001271951.2(TPGS2):c.800G>A(p.Arg267Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,234,394 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

TPGS2
NM_001271951.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.159

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048164725).

BP6

Variant 18-36786937-C-T is Benign according to our data. Variant chr18-36786937-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648681.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
TPGS2	NM_001271951.2 linkuse as main transcript	c.800G>A	p.Arg267Gln	missense_variant	7/7
TPGS2	XM_005258242.5 linkuse as main transcript	c.671G>A	p.Arg224Gln	missense_variant	6/6
TPGS2	XM_011525917.4 linkuse as main transcript	c.656G>A	p.Arg219Gln	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
TPGS2	ENST00000590842.5 linkuse as main transcript	c.800G>A	p.Arg267Gln	missense_variant	7/7	2	Q68CL5-5
TPGS2	ENST00000591906.5 linkuse as main transcript	c.*7G>A		3_prime_UTR_variant	6/6	3
TPGS2	ENST00000610723.4 linkuse as main transcript	c.*132G>A		3_prime_UTR_variant	5/5	3

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00152

AC:

AN:

6598

Hom.:

AF XY:

0.00221

AC XY:

AN XY:

3164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00485

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00149

AC:

1613

AN:

1082064

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

739

AN XY:

510886

show subpopulations

Gnomad4 AFR exome

AF:

0.0000434

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00320

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0116

Gnomad4 NFE exome

AF:

0.00133

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00219

AC:

333

AN:

152330

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00397

Hom.:

Bravo

AF:

0.00110

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ExAC

AF:

0.000849

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TPGS2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.5

DANN

Benign

0.62

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.44

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0048

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

Sift4G

Benign

0.41

Vest4

0.19

MVP

0.51

GERP RS

-1.7

gMVP

0.099

Splicing

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