rs10460585

Variant names:

• chr2-85328139-T-G
• rs10460585
• ENST00000398263.6:c.-177A>C

Variant summary

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

The ENST00000398263.6(TGOLN2):​c.-177A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 660,240 control chromosomes in the GnomAD database, including 152,550 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 (37375 hom., cov: 32)
  • Exomes 𝑓: 0.67 (115175 hom.)
• Consequence: TGOLN2 ENST00000398263.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 21 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]

ENSG00000290110 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398263.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	NM_006464.4	MANE Select	c.-177A>C		upstream_gene	N/A	NP_006455.2
	TGOLN2	NM_001368095.1		c.-177A>C		upstream_gene	N/A	NP_001355024.1	O43493-7
	TGOLN2	NM_001368096.1		c.-177A>C		upstream_gene	N/A	NP_001355025.1	A0A5F9UY30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGOLN2	ENST00000398263.6	TSL:1	c.-177A>C		5_prime_UTR	Exon 1 of 5	ENSP00000381312.2	O43493-4
	ENSG00000290110	ENST00000703002.2		n.56T>G		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000307411	ENST00000825767.1		n.210+1317T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105478 AN: 152018 Hom.: 37319 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.666 AC: 338635 AN: 508102 Hom.: 115175 Cov.: 6 AF XY: 0.669 AC XY: 177698 AN XY: 265606

African (AFR) AF: 0.790 AC: 10970 AN: 13894

American (AMR) AF: 0.802 AC: 18430 AN: 22988

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 10128 AN: 14934

East Asian (EAS) AF: 0.951 AC: 29749 AN: 31296

South Asian (SAS) AF: 0.732 AC: 36007 AN: 49210

European-Finnish (FIN) AF: 0.631 AC: 23363 AN: 37022

Middle Eastern (MID) AF: 0.743 AC: 1565 AN: 2106

European-Non Finnish (NFE) AF: 0.614 AC: 189557 AN: 308768

Other (OTH) AF: 0.677 AC: 18866 AN: 27884

GnomAD4 genome AF: 0.694 AC: 105596 AN: 152138 Hom.: 37375 Cov.: 32 AF XY: 0.699 AC XY: 51993 AN XY: 74358

African (AFR) AF: 0.787 AC: 32681 AN: 41534

American (AMR) AF: 0.760 AC: 11623 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3470

East Asian (EAS) AF: 0.960 AC: 4966 AN: 5174

South Asian (SAS) AF: 0.723 AC: 3482 AN: 4816

European-Finnish (FIN) AF: 0.624 AC: 6594 AN: 10572

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41608 AN: 67970

Other (OTH) AF: 0.705 AC: 1490 AN: 2112

Alfa AF: 0.651 Hom.: 37495

Bravo AF: 0.713

Asia WGS AF: 0.839 AC: 2916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		-0.50
PromoterAI		0.058	Neutral
Mutation Taster		=300/0	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

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

Other links and lift over

dbSNP: rs10460585;

hg19: chr2-85555262;