dbSNP rs776923642: GOLGA6B:p.Arg347Gln (chr15-72662444-G-A) – 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.1040G>A(p.Arg347Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.000055 ( 2 hom., cov: 20)

Exomes 𝑓: 0.00013 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA6B
NM_018652.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.92

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036625475).

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.1040G>A	p.Arg347Gln	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.1040G>A	p.Arg347Gln	missense_variant	Exon 11 of 18	1	NM_018652.5	ENSP00000408132.3		A6NDN3

Frequencies

GnomAD3 genomes

AF:

0.0000551

AC:

AN:

127044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000831

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:

0.0000700

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000415

AC:

AN:

216812

Hom.:

AF XY:

0.0000512

AC XY:

AN XY:

117144

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:

0.0000793

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000132

AC:

167

AN:

1266718

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

628020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000298

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.0000575

GnomAD4 genome

AF:

0.0000551

AC:

AN:

127044

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

61334

show subpopulations

Gnomad4 AFR

AF:

0.0000831

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:

0.0000700

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1040G>A (p.R347Q) alteration is located in exon 11 (coding exon 11) of the GOLGA6B gene. This alteration results from a G to A substitution at nucleotide position 1040, causing the arginine (R) at amino acid position 347 to be replaced by a glutamine (Q). 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

0.077

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.0

DANN

Benign

0.76

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.55

M_CAP

Benign

0.00095

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.63

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.18

REVEL

Benign

0.010

Sift

Benign

0.36

Sift4G

Benign

0.56

Polyphen

0.0010

Vest4

0.043

MutPred

0.30

Loss of MoRF binding (P = 0.0898);

MVP

0.014

ClinPred

0.053

Varity_R

0.032

gMVP

0.075

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