Variant 9-124880547-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002077.4(GOLGA1):c.2287C>T(p.Arg763Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000362 in 1,603,068 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

GOLGA1
NM_002077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

GOLGA1 (HGNC:4424): (golgin A1) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This encoded protein is associated with Sjogren's syndrome. [provided by RefSeq, Feb 2010]

GOLGA1 links:

GOLGA1 (HGNC:):

GOLGA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18471128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA1	NM_002077.4 linkuse as main transcript	c.2287C>T	p.Arg763Trp	missense_variant	23/23	ENST00000373555.9	NP_002068.2	Q92805A0A024R869

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GOLGA1	ENST00000373555.9 linkuse as main transcript	c.2287C>T	p.Arg763Trp	missense_variant	23/23	1	NM_002077.4	ENSP00000362656.4	Q92805
GOLGA1	ENST00000475407.5 linkuse as main transcript	n.*1433C>T		non_coding_transcript_exon_variant	18/18	5		ENSP00000473648.1	R4GNH1
GOLGA1	ENST00000475407.5 linkuse as main transcript	n.*1433C>T		3_prime_UTR_variant	18/18	5		ENSP00000473648.1	R4GNH1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000262

AC:

AN:

251432

Hom.:

AF XY:

0.000272

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000510

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000374

AC:

543

AN:

1450876

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

268

AN XY:

722610

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000468

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000243

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000515

Hom.:

Bravo

AF:

0.000321

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

The c.2287C>T (p.R763W) alteration is located in exon 23 (coding exon 21) of the GOLGA1 gene. This alteration results from a C to T substitution at nucleotide position 2287, causing the arginine (R) at amino acid position 763 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.025

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.18

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.037

Polyphen

1.0

Vest4

0.41

MVP

0.59

MPC

0.89

ClinPred

0.27

GERP RS

4.2

Varity_R

0.24

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over