Variant 15-34386701-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.209C>T(p.Pro70Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000095 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000072 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8A
NM_181077.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.418

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=0.04193133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA8A	NM_181077.5 linkuse as main transcript	c.209C>T	p.Pro70Leu	missense_variant	12/25	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.209C>T	p.Pro70Leu	missense_variant	12/25	1	NM_181077.5	ENSP00000352111.4	A7E2F4-3
GOLGA8A	ENST00000473125.5 linkuse as main transcript	n.2287C>T		non_coding_transcript_exon_variant	10/23	1
GOLGA8A	ENST00000699472.1 linkuse as main transcript	c.209C>T	p.Pro70Leu	missense_variant	12/25			ENSP00000514395.1	A0A8V8TPN8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137218

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000293

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000432

Gnomad SAS

AF:

0.000686

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000307

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000114

AC:

AN:

201284

Hom.:

AF XY:

0.000146

AC XY:

AN XY:

109926

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.0000391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000242

Gnomad SAS exome

AF:

0.000454

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000437

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000720

AC:

101

AN:

1402722

Hom.:

Cov.:

AF XY:

0.0000915

AC XY:

AN XY:

699304

show subpopulations

Gnomad4 AFR exome

AF:

0.000102

Gnomad4 AMR exome

AF:

0.0000244

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000433

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000191

Gnomad4 NFE exome

AF:

0.0000253

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000947

AC:

AN:

137218

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

66608

show subpopulations

Gnomad4 AFR

AF:

0.0000596

Gnomad4 AMR

AF:

0.000293

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000432

Gnomad4 SAS

AF:

0.000686

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000307

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000159

AC:

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

Oct 27, 2021

The c.209C>T (p.P70L) alteration is located in exon 3 (coding exon 3) of the GOLGA8A gene. This alteration results from a C to T substitution at nucleotide position 209, causing the proline (P) at amino acid position 70 to be replaced by a leucine (L). 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

0.086

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

4.8

DANN

Benign

0.65

DEOGEN2

Benign

0.054

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-4.8

.;D

REVEL

Benign

0.21

Sift

Benign

0.41

.;T

Sift4G

Benign

0.16

T;T

Polyphen

0.066

.;B

Vest4

0.26

MVP

0.082

ClinPred

0.038

GERP RS

-0.76

Varity_R

0.053

gMVP

0.11

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