NM_002078.5:c.62C>G

Variant summary

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

The NM_002078.5(GOLGA4):​c.62C>G​(p.Ala21Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GOLGA4
NM_002078.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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-AS1 (HGNC:26469): (GOLGA4 antisense RNA 1)

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=0.0905363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GOLGA4NM_002078.5 linkc.62C>G p.Ala21Gly missense_variant Exon 1 of 24 ENST00000361924.7 NP_002069.2 Q13439-1Q49A56

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GOLGA4ENST00000361924.7 linkc.62C>G p.Ala21Gly missense_variant Exon 1 of 24 1 NM_002078.5 ENSP00000354486.2 Q13439-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1460278
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
726534
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.62C>G (p.A21G) alteration is located in exon 1 (coding exon 1) of the GOLGA4 gene. This alteration results from a C to G substitution at nucleotide position 62, causing the alanine (A) at amino acid position 21 to be replaced by a glycine (G). 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
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
18
DANN
Benign
0.96
DEOGEN2
Benign
0.053
T;.;.;.;T;.
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.54
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.70
T;T;T;T;T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.091
T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.;L;.;.;.
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.2
N;N;N;N;N;D
REVEL
Benign
0.030
Sift
Benign
0.12
T;D;D;T;D;D
Sift4G
Benign
0.066
T;T;D;T;D;D
Polyphen
0.0020
B;B;.;B;.;.
Vest4
0.10
MutPred
0.085
Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);Loss of helix (P = 0.0138);
MVP
0.18
MPC
0.044
ClinPred
0.14
T
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.079
gMVP
0.087

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-37285103; API