Variant 2-85326595-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006464.4(TGOLN2):c.1137C>G(p.Ser379Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

TGOLN2
NM_006464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.689

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 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=0.14072701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TGOLN2	NM_006464.4 linkuse as main transcript	c.1137C>G	p.Ser379Arg	missense_variant	2/4	ENST00000377386.8	NP_006455.2
TGOLN2	NM_001368095.1 linkuse as main transcript	c.1137C>G	p.Ser379Arg	missense_variant	2/4		NP_001355024.1
TGOLN2	NM_001368096.1 linkuse as main transcript	c.1137C>G	p.Ser379Arg	missense_variant	2/4		NP_001355025.1
TGOLN2	NM_001206844.2 linkuse as main transcript	c.963C>G	p.Ser321Arg	missense_variant	3/5		NP_001193773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8 linkuse as main transcript	c.1137C>G	p.Ser379Arg	missense_variant	2/4	1	NM_006464.4	ENSP00000366603	A2	O43493-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000321

AC:

AN:

249206

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135218

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000493

AC:

AN:

1461680

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000639

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000248

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

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 11, 2023

The c.1137C>G (p.S379R) alteration is located in exon 2 (coding exon 2) of the TGOLN2 gene. This alteration results from a C to G substitution at nucleotide position 1137, causing the serine (S) at amino acid position 379 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

0.31

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

T;.;.;.;.;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.56

.;T;T;.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.;L;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

.;N;N;N;N;N

REVEL

Benign

0.099

Sift

Benign

0.060

.;T;D;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;T

Polyphen

0.84

P;P;P;.;.;P

Vest4

0.12

MutPred

0.24

Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);.;Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);

MVP

0.22

ClinPred

0.14

GERP RS

-2.1

Varity_R

0.067

gMVP

0.10

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

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