NM_018652.5:c.686G>A

Variant names:

• chr15-72661493-G-A
• rs1288129339
• NM_018652.5:c.686G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018652.5(GOLGA6B):​c.686G>A​(p.Arg229Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00010 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.34
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024456173).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018652.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	NM_018652.5	MANE Select	c.686G>A	p.Arg229Gln	missense	Exon 9 of 18	NP_061122.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6B	ENST00000421285.4	TSL:1 MANE Select	c.686G>A	p.Arg229Gln	missense	Exon 9 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.680G>A	p.Arg227Gln	missense	Exon 9 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.000127 AC: 18 AN: 141366 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000702

Gnomad ASJ AF: 0.00360

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000766

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000838 AC: 5 AN: 59700 AF XY: 0.0000669

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000907

Gnomad ASJ exome AF: 0.00128

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000811

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000101 AC: 117 AN: 1155920 Hom.: 0 Cov.: 18 AF XY: 0.000104 AC XY: 61 AN XY: 584280

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000374 AC: 1 AN: 26738

American (AMR) AF: 0.0000246 AC: 1 AN: 40648

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 54 AN: 23340

East Asian (EAS) AF: 0.00 AC: 0 AN: 38364

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37210

Middle Eastern (MID) AF: 0.00168 AC: 6 AN: 3576

European-Non Finnish (NFE) AF: 0.0000467 AC: 40 AN: 856484

Other (OTH) AF: 0.000278 AC: 14 AN: 50306

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000127 AC: 18 AN: 141476 Hom.: 0 Cov.: 21 AF XY: 0.000102 AC XY: 7 AN XY: 68666

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 36706

American (AMR) AF: 0.0000701 AC: 1 AN: 14270

Ashkenazi Jewish (ASJ) AF: 0.00360 AC: 12 AN: 3330

East Asian (EAS) AF: 0.00 AC: 0 AN: 4880

South Asian (SAS) AF: 0.00 AC: 0 AN: 4204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.0000766 AC: 5 AN: 65284

Other (OTH) AF: 0.00 AC: 0 AN: 1834

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000331009), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
PhyloP100		4.3
Varity_R		0.050
gMVP		0.54
Mutation Taster		=94/6	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1288129339; hg19: chr15-72953834;