15-72661459-G-A

Variant names:

• chr15-72661459-G-A
• rs1331661371
• NM_018652.5:c.652G>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.652G>A​(p.Val218Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000035 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0000031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense, splice_region
• Scores: Splicing: ADA: 0.0005927
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20
• 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=0.055187345).

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.652G>A	p.Val218Met	missense splice_region	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.652G>A	p.Val218Met	missense splice_region	Exon 9 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.646G>A	p.Val216Met	missense splice_region	Exon 9 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000347 AC: 5 AN: 144020 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000275

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000322 AC: 2 AN: 62042 AF XY: 0.0000324

Gnomad AFR exome AF: 0.000179

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000483

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000312 AC: 4 AN: 1282302 Hom.: 0 Cov.: 21 AF XY: 0.00000310 AC XY: 2 AN XY: 644244

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

African (AFR) AF: 0.0000342 AC: 1 AN: 29260

American (AMR) AF: 0.0000466 AC: 2 AN: 42898

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24428

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 82588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4022

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 964552

Other (OTH) AF: 0.0000183 AC: 1 AN: 54660

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00553722), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000347 AC: 5 AN: 144126 Hom.: 0 Cov.: 21 AF XY: 0.0000429 AC XY: 3 AN XY: 70008

African (AFR) AF: 0.0000264 AC: 1 AN: 37838

American (AMR) AF: 0.000275 AC: 4 AN: 14546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4882

South Asian (SAS) AF: 0.00 AC: 0 AN: 4358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66110

Other (OTH) AF: 0.00 AC: 0 AN: 1896

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	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.2
DANN	Benign	0.68
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	0.13	N
REVEL	Benign	0.028
Sift	Benign	0.17	T
Sift4G	Benign	0.24	T
Polyphen		0.0050	B
Vest4		0.16
MutPred		0.16		Gain of disorder (P = 0.0865)
MVP		0.030
ClinPred		0.027	T
GERP RS		-0.78
Varity_R		0.030
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00059
dbscSNV1_RF	Benign	0.11
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

Other links and lift over

dbSNP: rs1331661371; hg19: chr15-72953800;