rs7428

Positions:

• chr2-85318367-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006464.4(TGOLN2):​c.*4369A>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_006464.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGOLN2	NM_006464.4	c.*4369A>G		3_prime_UTR_variant	4/4	ENST00000377386.8	NP_006455.2
TGOLN2	NM_001368095.1	c.*4376A>G		3_prime_UTR_variant	4/4		NP_001355024.1
TGOLN2	NM_001368096.1	c.*4338A>G		3_prime_UTR_variant	4/4		NP_001355025.1
TGOLN2	NM_001206844.2	c.*4369A>G		3_prime_UTR_variant	5/5		NP_001193773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8	c.*4369A>G		3_prime_UTR_variant	4/4	1	NM_006464.4	ENSP00000366603.3
TGOLN2	ENST00000398263.6	c.*4369A>G		3_prime_UTR_variant	5/5	1		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

Gnomad4 NFE exome AF: 0.571

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

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.370

Alfa AF: 0.387 Hom.: 19764

Bravo AF: 0.335

Asia WGS AF: 0.490 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Other links and lift over

dbSNP: rs7428; hg19: chr2-85545490;