Variant 15-34385767-C-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.297G>T(p.Lys99Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 18)

Exomes 𝑓: 0.00036 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8A
NM_181077.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.288

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:

GOLGA8A (HGNC:):

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=0.037379295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA8A	NM_181077.5 linkuse as main transcript	c.297G>T	p.Lys99Asn	missense_variant	13/25	ENST00000359187.5	NP_851422.1	A7E2F4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GOLGA8A	ENST00000359187.5 linkuse as main transcript	c.297G>T	p.Lys99Asn	missense_variant	13/25	1	NM_181077.5	ENSP00000352111.4	A7E2F4-3
GOLGA8A	ENST00000473125.5 linkuse as main transcript	n.2375G>T		non_coding_transcript_exon_variant	11/23	1
GOLGA8A	ENST00000699472.1 linkuse as main transcript	c.297G>T	p.Lys99Asn	missense_variant	13/25			ENSP00000514395.1	A0A8V8TPN8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

119720

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000885

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:

0.000583

Gnomad OTH

AF:

0.000622

GnomAD3 exomes

AF:

0.000416

AC:

AN:

57754

Hom.:

AF XY:

0.000416

AC XY:

AN XY:

28874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000980

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000362

AC:

320

AN:

884314

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

156

AN XY:

457362

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:

0.000494

Gnomad4 OTH exome

AF:

0.000293

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000326

AC:

AN:

119720

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

AN XY:

57640

show subpopulations

Gnomad4 AFR

AF:

0.0000885

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:

0.000583

Gnomad4 OTH

AF:

0.000622

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

Aug 27, 2024

The c.297G>T (p.K99N) alteration is located in exon 4 (coding exon 4) of the GOLGA8A gene. This alteration results from a G to T substitution at nucleotide position 297, causing the lysine (K) at amino acid position 99 to be replaced by an asparagine (N). 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

Uncertain

0.51

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.62

DEOGEN2

Benign

0.0085

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.47

N;.

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.3

.;D

REVEL

Benign

0.094

Sift

Benign

0.26

.;T

Sift4G

Benign

0.10

T;T

Polyphen

0.025

.;B

Vest4

0.067

MutPred

0.46

.;Loss of ubiquitination at K99 (P = 0.0118);

MVP

0.20

ClinPred

0.036

GERP RS

-0.76

Varity_R

0.077

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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