rs201343526

Variant names:

• chr15-72661298-G-A
• rs201343526
• NM_018652.5:c.599G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018652.5(GOLGA6B):​c.599G>A​(p.Arg200Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 152,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R200W) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00018 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013325483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA6B	NM_018652.5	c.599G>A	p.Arg200Gln	missense_variant	Exon 8 of 18	ENST00000421285.4	NP_061122.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA6B	ENST00000421285.4	c.599G>A	p.Arg200Gln	missense_variant	Exon 8 of 18	1	NM_018652.5	ENSP00000408132.3

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 151900 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000369 AC: 91 AN: 246402 Hom.: 0 AF XY: 0.000352 AC XY: 47 AN XY: 133620

Gnomad AFR exome AF: 0.00147

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.000393

Gnomad FIN exome AF: 0.000142

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.000499

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000182 AC: 265 AN: 1455012 Hom.: 1 Cov.: 31 AF XY: 0.000174 AC XY: 126 AN XY: 723820

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000302

Gnomad4 FIN exome AF: 0.000114

Gnomad4 NFE exome AF: 0.000148

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome AF: 0.000329 AC: 50 AN: 152018 Hom.: 0 Cov.: 24 AF XY: 0.000336 AC XY: 25 AN XY: 74378

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000912 Hom.: 0

ESP6500AA AF: 0.000672 AC: 2

ESP6500EA AF: 0.000376 AC: 2

ExAC AF: 0.00152 AC: 184

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.599G>A (p.R200Q) alteration is located in exon 8 (coding exon 8) of the GOLGA6B gene. This alteration results from a G to A substitution at nucleotide position 599, causing the arginine (R) at amino acid position 200 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	0.071
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.74
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00083	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.93	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.030
Sift	Benign	0.93	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	B
Vest4		0.14
MVP		0.014
ClinPred		0.0028	T
GERP RS		-0.78
Varity_R		0.017
gMVP		0.071

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

Other links and lift over

dbSNP: rs201343526; hg19: chr15-72953639;