Variant 3-37251463-T-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_002078.5(GOLGA4):c.141T>A(p.Asp47Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000792 in 1,607,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 1 hom. )

Consequence

GOLGA4
NM_002078.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.485

Variant links:

Genes affected

GOLGA4 (HGNC:4427): (golgin A4) 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 protein has been postulated to play a role in Rab6-regulated membrane-tethering events in the Golgi apparatus. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2010]

GOLGA4 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=0.016919106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA4	NM_002078.5 link	c.141T>A	p.Asp47Glu	missense_variant	2/24	ENST00000361924.7	NP_002069.2	Q13439-1Q49A56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA4	ENST00000361924.7 link	c.141T>A	p.Asp47Glu	missense_variant	2/24	1	NM_002078.5	ENSP00000354486.2		Q13439-1

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000394

AC:

AN:

251334

Hom.:

AF XY:

0.000405

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000971

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000826

AC:

1202

AN:

1455586

Hom.:

Cov.:

AF XY:

0.000781

AC XY:

566

AN XY:

724628

show subpopulations

Gnomad4 AFR exome

AF:

0.000150

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000843

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000366

GnomAD4 genome

AF:

0.000473

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000737

Hom.:

Bravo

AF:

0.000468

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000387

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000889

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

Dec 05, 2024

The c.141T>A (p.D47E) alteration is located in exon 2 (coding exon 2) of the GOLGA4 gene. This alteration results from a T to A substitution at nucleotide position 141, causing the aspartic acid (D) at amino acid position 47 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.58

DEOGEN2

Benign

0.10

T;.;.;.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.68

T;T;T;T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.017

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;.;L;.;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

N;N;N;N;N;D

REVEL

Benign

0.050

Sift

Benign

0.052

T;T;T;D;D;T

Sift4G

Benign

0.25

T;T;T;T;T;D

Polyphen

0.058

B;B;.;B;.;.

Vest4

0.31

MutPred

0.10

Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);

MVP

0.21

MPC

0.047

ClinPred

0.025

GERP RS

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.068

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