Genetic Variant GOLGA6B:p.Arg208Gln (chr15-72661322-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_018652.5(GOLGA6B):c.623G>A(p.Arg208Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00649 in 151,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 1 hom., cov: 24)

Exomes 𝑓: 0.0083 ( 26 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6B
NM_018652.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.978

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055083334).

BP6

Variant 15-72661322-G-A is Benign according to our data. Variant chr15-72661322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3341557.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6B	NM_018652.5 link	c.623G>A	p.Arg208Gln	missense_variant	Exon 8 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.623G>A	p.Arg208Gln	missense_variant	Exon 8 of 18	1	NM_018652.5	ENSP00000408132.3		A6NDN3

Frequencies

GnomAD3 genomes

AF:

0.00649

AC:

986

AN:

151828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00301

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00476

AC:

1171

AN:

245914

Hom.:

AF XY:

0.00483

AC XY:

645

AN XY:

133460

show subpopulations

Gnomad AFR exome

AF:

0.00138

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00951

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.00228

Gnomad NFE exome

AF:

0.00758

Gnomad OTH exome

AF:

0.00596

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00831

AC:

12068

AN:

1452372

Hom.:

Cov.:

AF XY:

0.00847

AC XY:

6123

AN XY:

722558

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.0118

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00433

Gnomad4 FIN exome

AF:

0.00379

Gnomad4 NFE exome

AF:

0.00953

Gnomad4 OTH exome

AF:

0.00784

GnomAD4 genome

AF:

0.00649

AC:

986

AN:

151946

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

442

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00150

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.0144

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00301

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.0105

Hom.:

ExAC

AF:

0.00776

AC:

938

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GOLGA6B: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

DANN

Benign

0.60

DEOGEN2

Benign

0.0034

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.93

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.91

REVEL

Benign

0.038

Sift

Benign

0.54

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.21

MVP

0.030

ClinPred

0.0019

GERP RS

-0.78

Varity_R

0.025

gMVP

0.22

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