Genetic Variant TGOLN2:c.*1220T>C (chr2-85321516-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006464.4(TGOLN2):c.*1220T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,552 control chromosomes in the GnomAD database, including 36,822 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 36734 hom., cov: 32)

Exomes 𝑓: 0.65 ( 88 hom. )

Consequence

TGOLN2
NM_006464.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.308

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TGOLN2	NM_006464.4 link	c.*1220T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000377386.8	NP_006455.2	O43493-2
TGOLN2	NM_001368095.1 link	c.*1227T>C	3_prime_UTR_variant	Exon 4 of 4		NP_001355024.1
TGOLN2	NM_001368096.1 link	c.*1189T>C	3_prime_UTR_variant	Exon 4 of 4		NP_001355025.1
TGOLN2	NM_001206844.2 link	c.*1220T>C	3_prime_UTR_variant	Exon 5 of 5		NP_001193773.1	O43493-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8 link	c.*1220T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_006464.4	ENSP00000366603.3		O43493-2
TGOLN2	ENST00000398263.6 link	c.*1220T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000381312.2		O43493-4

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104296

AN:

151998

Hom.:

36674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.576

Gnomad AMR

AF:

0.750

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.960

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.692

GnomAD4 exome

AF:

0.647

AC:

281

AN:

434

Hom.:

Cov.:

AF XY:

0.650

AC XY:

169

AN XY:

260

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.651

AC:

276

AN:

424

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.686

AC:

104418

AN:

152118

Hom.:

36734

Cov.:

AF XY:

0.691

AC XY:

51365

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.800

AC:

33195

AN:

41498

American (AMR)

AF:

0.750

AC:

11458

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

2388

AN:

3470

East Asian (EAS)

AF:

0.960

AC:

4973

AN:

5182

South Asian (SAS)

AF:

0.697

AC:

3364

AN:

4826

European-Finnish (FIN)

AF:

0.611

AC:

6457

AN:

10564

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.594

AC:

40364

AN:

67988

Other (OTH)

AF:

0.695

AC:

1467

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1649

3297

4946

6594

8243

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

802

1604

2406

3208

4010

<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:

0.636

Hom.:

40957

Bravo

AF:

0.706

Asia WGS

AF:

0.828

AC:

2877

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.1

(source)

DANN

Benign

0.55

PhyloP100

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over