Variant rs4247303 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006464.4(TGOLN2):c.775C>T(p.Arg259Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,613,742 control chromosomes in the GnomAD database, including 216,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.49 ( 19546 hom., cov: 32)

Exomes 𝑓: 0.51 ( 197359 hom. )

Consequence

TGOLN2
NM_006464.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.30

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.579028E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGOLN2	NM_006464.4 linkuse as main transcript	c.775C>T	p.Arg259Trp	missense_variant	2/4	ENST00000377386.8	NP_006455.2	O43493-2
TGOLN2	NM_001368095.1 linkuse as main transcript	c.775C>T	p.Arg259Trp	missense_variant	2/4		NP_001355024.1
TGOLN2	NM_001368096.1 linkuse as main transcript	c.775C>T	p.Arg259Trp	missense_variant	2/4		NP_001355025.1
TGOLN2	NM_001206844.2 linkuse as main transcript	c.753+22C>T		intron_variant			NP_001193773.1	O43493-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8 linkuse as main transcript	c.775C>T	p.Arg259Trp	missense_variant	2/4	1	NM_006464.4	ENSP00000366603.3		O43493-2

Frequencies

GnomAD3 genomes

AF:

0.493

AC:

74946

AN:

151926

Hom.:

19532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.512

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.874

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.537

GnomAD3 exomes

AF:

0.569

AC:

141847

AN:

249228

Hom.:

42640

AF XY:

0.569

AC XY:

76905

AN XY:

135206

show subpopulations

Gnomad AFR exome

AF:

0.357

Gnomad AMR exome

AF:

0.716

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.883

Gnomad SAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.551

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.513

AC:

749212

AN:

1461698

Hom.:

197359

Cov.:

AF XY:

0.516

AC XY:

375140

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.706

Gnomad4 ASJ exome

AF:

0.599

Gnomad4 EAS exome

AF:

0.858

Gnomad4 SAS exome

AF:

0.615

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.484

Gnomad4 OTH exome

AF:

0.536

GnomAD4 genome

AF:

0.493

AC:

74983

AN:

152044

Hom.:

19546

Cov.:

AF XY:

0.504

AC XY:

37429

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.361

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.612

Gnomad4 EAS

AF:

0.873

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.557

Gnomad4 NFE

AF:

0.488

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.507

Hom.:

36076

Bravo

AF:

0.497

TwinsUK

AF:

0.492

AC:

1824

ALSPAC

AF:

0.478

AC:

1842

ESP6500AA

AF:

0.357

AC:

1390

ESP6500EA

AF:

0.494

AC:

4087

ExAC

AF:

0.558

AC:

67441

Asia WGS

AF:

0.730

AC:

2536

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.033

T;.;.;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.59

.;T;.;T;T

MetaRNN

Benign

9.6e-7

T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.2

L;L;L;.;L

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.0

.;N;N;N;N

REVEL

Benign

0.081

Sift

Uncertain

0.013

.;D;D;T;D

Sift4G

Uncertain

0.017

D;D;D;D;D

Polyphen

1.0

D;D;.;.;D

Vest4

0.039

ClinPred

0.053

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.040

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over