Genetic Variant GOLGA6B:p.Ala289Val (chr15-72662270-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018652.5(GOLGA6B):c.866C>T(p.Ala289Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000881 in 1,384,176 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000074 ( 2 hom., cov: 19)

Exomes 𝑓: 0.000089 ( 33 hom. )

Consequence

GOLGA6B
NM_018652.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.246

Variant links:

Genes affected

GOLGA6B (HGNC:32205): (golgin A6 family member B) This gene is found in a large, low copy repeat sequence or duplicon that is found in multiple copies, which are greater than 90% similar, on chromosome 15. Duplicons are associated with deletions, inversions and other chromosomal rearrangements that underlie genomic disease. This gene is a member of the golgin gene family, whose protein products localize to the Golgi apparatus. The majority of the related gene copies are thought to be transcribed pseudogenes. It is not known whether this gene is a pseudogene or if it encodes a golgin protein. [provided by RefSeq, Jul 2008]

GOLGA6B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.025268495).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6B	NM_018652.5 link	c.866C>T	p.Ala289Val	missense_variant	Exon 11 of 18	ENST00000421285.4	NP_061122.4	A6NDN3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6B	ENST00000421285.4 link	c.866C>T	p.Ala289Val	missense_variant	Exon 11 of 18	1	NM_018652.5	ENSP00000408132.3		A6NDN3

Frequencies

GnomAD3 genomes

AF:

0.0000745

AC:

AN:

120870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000857

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:

0.000127

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000176

AC:

AN:

215662

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

116610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000288

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000400

Gnomad FIN exome

AF:

0.000379

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.000188

GnomAD4 exome

AF:

0.0000894

AC:

113

AN:

1263306

Hom.:

Cov.:

AF XY:

0.0000799

AC XY:

AN XY:

626028

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000302

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000881

Gnomad4 SAS exome

AF:

0.000205

Gnomad4 FIN exome

AF:

0.000352

Gnomad4 NFE exome

AF:

0.0000589

Gnomad4 OTH exome

AF:

0.000154

GnomAD4 genome

AF:

0.0000745

AC:

AN:

120870

Hom.:

Cov.:

AF XY:

0.0000519

AC XY:

AN XY:

57846

show subpopulations

Gnomad4 AFR

AF:

0.0000291

Gnomad4 AMR

AF:

0.0000857

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000127

Gnomad4 OTH

AF:

0.00

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000267

AC:

ExAC

AF:

0.000192

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 14, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.866C>T (p.A289V) alteration is located in exon 11 (coding exon 11) of the GOLGA6B gene. This alteration results from a C to T substitution at nucleotide position 866, causing the alanine (A) at amino acid position 289 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

0.079

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.0032

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.22

M_CAP

Benign

0.0014

MetaRNN

Benign

0.025

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.3

REVEL

Benign

0.079

Sift

Benign

0.20

Sift4G

Benign

0.19

Polyphen

0.0

Vest4

0.073

MVP

0.014

ClinPred

0.0099

GERP RS

-1.4

Varity_R

0.025

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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