rs4247303

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is The variant received -5 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_StrongB3_Supporting

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 cumulative frequency of 0.511 (AC=824,195) in the gnomAD database across 1,613,742 control chromosomes, including 216,905 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.852. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.R259P: Uncertain_significance (ClinVar VariationId 3325767, 1 star) The variant has been observed in cBioPortal in 4 samples across 4 studies and 4 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

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

Publications

53 publications found

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:

ENSG00000307411 (HGNC:):

ENSG00000307411 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_006464.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 points.

GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.852 — exceeds 1% threshold (B1 applied)

Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006464.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGOLN2	NM_006464.4	MANE Select	c.775C>T	p.Arg259Trp	missense	Exon 2 of 4	NP_006455.2
TGOLN2	NM_001368095.1		c.775C>T	p.Arg259Trp	missense	Exon 2 of 4	NP_001355024.1	O43493-7
TGOLN2	NM_001368096.1		c.775C>T	p.Arg259Trp	missense	Exon 2 of 4	NP_001355025.1	A0A5F9UY30

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGOLN2	ENST00000377386.8	TSL:1 MANE Select	c.775C>T	p.Arg259Trp	missense	Exon 2 of 4	ENSP00000366603.3	O43493-2
TGOLN2	ENST00000409015.5	TSL:1	c.775C>T	p.Arg259Trp	missense	Exon 2 of 4	ENSP00000387035.1	O43493-7
TGOLN2	ENST00000409232.7	TSL:1	c.775C>T	p.Arg259Trp	missense	Exon 2 of 4	ENSP00000386443.3	A0A5F9UY30

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

GnomAD2 exomes

AF:

0.569

AC:

141847

AN:

249228

AF XY:

0.569

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 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

African (AFR)

AF:

0.353

AC:

11824

AN:

33480

American (AMR)

AF:

0.706

AC:

31554

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

15650

AN:

26136

East Asian (EAS)

AF:

0.858

AC:

34069

AN:

39700

South Asian (SAS)

AF:

0.615

AC:

53089

AN:

86258

European-Finnish (FIN)

AF:

0.550

AC:

29395

AN:

53398

Middle Eastern (MID)

AF:

0.626

AC:

3609

AN:

5768

European-Non Finnish (NFE)

AF:

0.484

AC:

537660

AN:

1111860

Other (OTH)

AF:

0.536

AC:

32362

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

25578

51157

76735

102314

127892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15976

31952

47928

63904

79880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.493

AC:

74983

AN:

152044

Hom.:

19546

Cov.:

AF XY:

0.504

AC XY:

37429

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.361

AC:

14962

AN:

41476

American (AMR)

AF:

0.627

AC:

9588

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

2124

AN:

3470

East Asian (EAS)

AF:

0.873

AC:

4510

AN:

5164

South Asian (SAS)

AF:

0.610

AC:

2933

AN:

4812

European-Finnish (FIN)

AF:

0.557

AC:

5888

AN:

10572

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33193

AN:

67952

Other (OTH)

AF:

0.539

AC:

1138

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1909

3817

5726

7634

9543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

666

1332

1998

2664

3330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.503

Hom.:

77758

Bravo

AF:

0.497

Asia WGS

AF:

0.730

AC:

2536

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.834

AC:

102390

AN:

122780

Turkish Variome

AF:

0.599

AC:

4031

AN:

6724

Hom.:

1221

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.880

AC:

7889

AN:

8960

Hom.:

3472

ABraOM SABE-WGS-1171

AF:

0.514

AC:

1204

AN:

2342

Hom.:

328

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.033

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.59

MetaRNN

Benign

9.6e-7

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.2

PhyloP100

-5.3

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.0

REVEL

Benign

0.081

Sift

Uncertain

0.013

Sift4G

Uncertain

0.017

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.052

gMVP

0.040

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over