Variant 3-121669213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366282.2(GOLGB1):c.9320C>T(p.Ala3107Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000839 in 1,613,148 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00088 ( 1 hom. )

Consequence

GOLGB1
NM_001366282.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.812

Variant links:

Genes affected

GOLGB1 (HGNC:4429): (golgin B1) Enables RNA binding activity. Involved in protein localization to pericentriolar material. Located in Golgi apparatus and endoplasmic reticulum-Golgi intermediate compartment. [provided by Alliance of Genome Resources, Apr 2022]

GOLGB1 links:

GOLGB1 (HGNC:):

GOLGB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010924935).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGB1	NM_001366282.2 linkuse as main transcript	c.9320C>T	p.Ala3107Val	missense_variant, splice_region_variant	18/22	ENST00000614479.5	NP_001353211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGB1	ENST00000614479.5 linkuse as main transcript	c.9320C>T	p.Ala3107Val	missense_variant, splice_region_variant	18/22	1	NM_001366282.2	ENSP00000484083.2		A0A8J9C4H3

Frequencies

GnomAD3 genomes

AF:

0.000434

AC:

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000567

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000594

AC:

149

AN:

250964

Hom.:

AF XY:

0.000671

AC XY:

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000960

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000882

AC:

1288

AN:

1461022

Hom.:

Cov.:

AF XY:

0.000850

AC XY:

618

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.000434

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.000567

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000696

Hom.:

Bravo

AF:

0.000427

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000659

AC:

EpiCase

AF:

0.000928

EpiControl

AF:

0.00142

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

May 09, 2023

The c.9305C>T (p.A3102V) alteration is located in exon 18 (coding exon 17) of the GOLGB1 gene. This alteration results from a C to T substitution at nucleotide position 9305, causing the alanine (A) at amino acid position 3102 to be replaced by a valine (V). 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

0.076

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.62

N;N;.

REVEL

Benign

0.081

Sift

Benign

0.086

T;T;.

Sift4G

Uncertain

0.016

D;T;D

Polyphen

0.89

P;.;.

Vest4

0.060

MVP

0.30

MPC

0.10

ClinPred

0.024

GERP RS

0.60

Varity_R

0.019

gMVP

0.048

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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