NM_002078.5:c.74C>T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002078.5(GOLGA4):c.74C>T(p.Ala25Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000674 in 1,602,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A25E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

GOLGA4
NM_002078.5 missense, splice_region

Scores

Splicing: ADA: 0.01311

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

2 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06292993).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002078.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLGA4	NM_002078.5	MANE Select	c.74C>T	p.Ala25Val	missense splice_region	Exon 2 of 24	NP_002069.2
GOLGA4	NM_001429190.1		c.74C>T	p.Ala25Val	missense splice_region	Exon 2 of 24	NP_001416119.1
GOLGA4	NM_001429191.1		c.74C>T	p.Ala25Val	missense splice_region	Exon 2 of 25	NP_001416120.1	A0A8V8TQI6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLGA4	ENST00000361924.7	TSL:1 MANE Select	c.74C>T	p.Ala25Val	missense splice_region	Exon 2 of 24	ENSP00000354486.2	Q13439-1
GOLGA4	ENST00000437131.2	TSL:1	c.74C>T	p.Ala25Val	missense splice_region	Exon 2 of 24	ENSP00000405842.2	H0Y6I0
GOLGA4	ENST00000356847.8	TSL:1	c.74C>T	p.Ala25Val	missense splice_region	Exon 2 of 23	ENSP00000349305.4	Q13439-5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000557

AC:

AN:

251124

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000690

AC:

100

AN:

1449918

Hom.:

Cov.:

AF XY:

0.0000651

AC XY:

AN XY:

722142

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33202

American (AMR)

AF:

0.0000224

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26022

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39636

South Asian (SAS)

AF:

0.0000581

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000799

AC:

AN:

1101218

Other (OTH)

AF:

0.0000500

AC:

AN:

60030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000342

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.79

M_CAP

Benign

0.0076

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

1.6

PrimateAI

Benign

0.46

PROVEAN

Benign

0.19

REVEL

Benign

0.012

Sift

Benign

0.40

Sift4G

Benign

0.36

Polyphen

0.58

Vest4

0.21

MVP

0.18

MPC

0.044

ClinPred

0.059

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.033

gMVP

0.086

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.013

dbscSNV1_RF

Benign

0.27

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over