Variant chr15-34381823-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181077.5(GOLGA8A):c.1487C>T(p.Ala496Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.00023 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000035 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8A
NM_181077.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.331

Variant links:

Genes affected

GOLGA8A (HGNC:31972): (golgin A8 family member A) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked, flattened membrane sacs referred to as cisternae. Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. The golgins constitute a family of proteins which are localized to the Golgi. This gene encodes a golgin which structurally resembles its family member GOLGA2, suggesting that they may share a similar function. There are many similar copies of this gene on chromosome 15. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

GOLGA8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032642007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA8A	NM_181077.5 linkuse as main transcript	c.1487C>T	p.Ala496Val	missense_variant	24/25	ENST00000359187.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA8A	ENST00000359187.5 linkuse as main transcript	c.1487C>T	p.Ala496Val	missense_variant	24/25	1	NM_181077.5	P4	A7E2F4-3
GOLGA8A	ENST00000473125.5 linkuse as main transcript	n.3565C>T		non_coding_transcript_exon_variant	22/23	1
GOLGA8A	ENST00000699472.1 linkuse as main transcript	c.1484C>T	p.Ala495Val	missense_variant	24/25			A2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

82230

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000703

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000113

AC:

AN:

62198

Hom.:

AF XY:

0.000127

AC XY:

AN XY:

31392

show subpopulations

Gnomad AFR exome

AF:

0.000887

Gnomad AMR exome

AF:

0.0000735

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000350

AC:

AN:

600762

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

311438

show subpopulations

Gnomad4 AFR exome

AF:

0.000516

Gnomad4 AMR exome

AF:

0.0000707

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:

0.0000233

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000231

AC:

AN:

82230

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

38498

show subpopulations

Gnomad4 AFR

AF:

0.000703

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000638

Hom.:

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 29, 2022

The c.1487C>T (p.A496V) alteration is located in exon 15 (coding exon 15) of the GOLGA8A gene. This alteration results from a C to T substitution at nucleotide position 1487, causing the alanine (A) at amino acid position 496 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

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.28

DANN

Benign

0.56

DEOGEN2

Benign

0.0030

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.037

Sift

Benign

0.29

.;T

Sift4G

Benign

0.60

T;T

Polyphen

0.11

B;P

Vest4

0.096

MutPred

0.38

Gain of sheet (P = 0.0028);.;

MVP

0.043

ClinPred

0.0049

GERP RS

-0.60

Varity_R

0.017

gMVP

0.052

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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