Variant 2-85327016-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006464.4(TGOLN2):c.716G>T(p.Gly239Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TGOLN2
NM_006464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.74

Variant links:

Genes affected

TGOLN2 (HGNC:15450): (trans-golgi network protein 2) This gene encodes a type I integral membrane protein that is localized to the trans-Golgi network, a major sorting station for secretory and membrane proteins. The encoded protein cycles between early endosomes and the trans-Golgi network, and may play a role in exocytic vesicle formation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

TGOLN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033337444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TGOLN2	NM_006464.4 linkuse as main transcript	c.716G>T	p.Gly239Val	missense_variant	2/4	ENST00000377386.8	NP_006455.2
TGOLN2	NM_001368095.1 linkuse as main transcript	c.716G>T	p.Gly239Val	missense_variant	2/4		NP_001355024.1
TGOLN2	NM_001368096.1 linkuse as main transcript	c.716G>T	p.Gly239Val	missense_variant	2/4		NP_001355025.1
TGOLN2	NM_001206844.2 linkuse as main transcript	c.716G>T	p.Gly239Val	missense_variant	2/5		NP_001193773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8 linkuse as main transcript	c.716G>T	p.Gly239Val	missense_variant	2/4	1	NM_006464.4	ENSP00000366603	A2	O43493-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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

Dec 13, 2023

The c.716G>T (p.G239V) alteration is located in exon 2 (coding exon 2) of the TGOLN2 gene. This alteration results from a G to T substitution at nucleotide position 716, causing the glycine (G) at amino acid position 239 to be replaced by a valine (V). 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

0.094

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.77

DANN

Benign

0.37

DEOGEN2

Benign

0.016

T;.;.;.;.;.

Eigen

Benign

-2.5

Eigen_PC

Benign

-2.7

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.50

.;T;T;.;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.033

T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.0

L;L;L;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

-2.2

.;N;N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.14

.;T;T;T;T;T

Sift4G

Benign

0.082

T;T;T;T;T;T

Polyphen

0.83

P;B;D;.;.;P

Vest4

0.074

MutPred

0.22

Loss of glycosylation at S238 (P = 0.0358);Loss of glycosylation at S238 (P = 0.0358);Loss of glycosylation at S238 (P = 0.0358);Loss of glycosylation at S238 (P = 0.0358);Loss of glycosylation at S238 (P = 0.0358);Loss of glycosylation at S238 (P = 0.0358);

MVP

0.088

ClinPred

0.18

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.046

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over