rs4247303

Variant names:

• chr2-85326957-G-A
• rs4247303
• NM_006464.4:c.775C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-85326957-G-A
• chr2-85326957-G-C

Variant summary

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

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 frequency of 0.511 in 1,613,742 control chromosomes in the GnomAD database, including 216,905 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R259P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.49 (19546 hom., cov: 32)
  • Exomes 𝑓: 0.51 (197359 hom.)
• Consequence: TGOLN2 NM_006464.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.30
• Publications: 52 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]

ENSG00000307411 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=9.579028E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGOLN2	NM_006464.4	c.775C>T	p.Arg259Trp	missense_variant	Exon 2 of 4	ENST00000377386.8	NP_006455.2
TGOLN2	NM_001368095.1	c.775C>T	p.Arg259Trp	missense_variant	Exon 2 of 4		NP_001355024.1
TGOLN2	NM_001368096.1	c.775C>T	p.Arg259Trp	missense_variant	Exon 2 of 4		NP_001355025.1
TGOLN2	NM_001206844.2	c.753+22C>T		intron_variant	Intron 2 of 4		NP_001193773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGOLN2	ENST00000377386.8	c.775C>T	p.Arg259Trp	missense_variant	Exon 2 of 4	1	NM_006464.4	ENSP00000366603.3

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74946 AN: 151926 Hom.: 19532 Cov.: 32

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

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.: 88 AF XY: 0.516 AC XY: 375140 AN XY: 727124

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

GnomAD4 genome AF: 0.493 AC: 74983 AN: 152044 Hom.: 19546 Cov.: 32 AF XY: 0.504 AC XY: 37429 AN XY: 74286

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

Alfa AF: 0.503 Hom.: 77758

Bravo AF: 0.497

TwinsUK AF: 0.492 AC: 1824

ALSPAC AF: 0.478 AC: 1842

ESP6500AA AF: 0.357 AC: 1390

ESP6500EA AF: 0.494 AC: 4087

ExAC AF: 0.558 AC: 67441

Asia WGS AF: 0.730 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.033	T;.;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.59	.;T;.;T;T
MetaRNN	Benign	9.6e-7	T;T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.2	L;L;L;.;L
PhyloP100		-5.3
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	.;N;N;N;N
REVEL	Benign	0.081
Sift	Uncertain	0.013	.;D;D;T;D
Sift4G	Uncertain	0.017	D;D;D;D;D
Polyphen		1.0	D;D;.;.;D
Vest4		0.039
ClinPred		0.053	T
GERP RS		-3.7
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)

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: rs4247303; hg19: chr2-85554080; COSMIC: COSV56407625;