rs7428

Variant names:

• chr2-85318367-T-C
• rs7428
• NM_006464.4:c.*4369A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368095.1(TGOLN2):​c.*4376A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,128 control chromosomes in the GnomAD database, including 10,069 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 0.33 (10067 hom., cov: 33)
  • Exomes 𝑓: 0.57 (2 hom.)
• Consequence: TGOLN2 NM_001368095.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 18 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368095.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	NM_006464.4	MANE Select	c.*4369A>G		3_prime_UTR	Exon 4 of 4	NP_006455.2
	TGOLN2	NM_001368095.1		c.*4376A>G		3_prime_UTR	Exon 4 of 4	NP_001355024.1
	TGOLN2	NM_001368096.1		c.*4338A>G		3_prime_UTR	Exon 4 of 4	NP_001355025.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	ENST00000377386.8	TSL:1 MANE Select	c.*4369A>G		3_prime_UTR	Exon 4 of 4	ENSP00000366603.3
	TGOLN2	ENST00000398263.6	TSL:1	c.*4369A>G		3_prime_UTR	Exon 5 of 5	ENSP00000381312.2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50710 AN: 151996 Hom.: 10049 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.571 AC: 8 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.600 AC XY: 6 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.571 AC: 8 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.334 AC: 50733 AN: 152114 Hom.: 10067 Cov.: 33 AF XY: 0.341 AC XY: 25372 AN XY: 74366

African (AFR) AF: 0.118 AC: 4914 AN: 41514

American (AMR) AF: 0.519 AC: 7934 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2635 AN: 5162

South Asian (SAS) AF: 0.459 AC: 2213 AN: 4824

European-Finnish (FIN) AF: 0.410 AC: 4332 AN: 10568

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25786 AN: 67982

Other (OTH) AF: 0.370 AC: 783 AN: 2116

Alfa AF: 0.373 Hom.: 42114

Bravo AF: 0.335

Asia WGS AF: 0.490 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		0.075
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7428; hg19: chr2-85545490;