chr15-72662530-G-A

Variant names:

• chr15-72662530-G-A
• rs1156764390
• NM_018652.5:c.1126G>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.1126G>A​(p.Glu376Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0000053 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6B NM_018652.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• 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=0.055626273).

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.1126G>A	p.Glu376Lys	missense	Exon 11 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.1126G>A	p.Glu376Lys	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.1120G>A	p.Glu374Lys	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes AF: 0.0000466 AC: 6 AN: 128754 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.000165

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000308 AC: 2 AN: 64898 AF XY: 0.00

Gnomad AFR exome AF: 0.000175

Gnomad AMR exome AF: 0.0000985

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: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000527 AC: 7 AN: 1329078 Hom.: 0 Cov.: 34 AF XY: 0.00000151 AC XY: 1 AN XY: 661614

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

African (AFR) AF: 0.0000944 AC: 3 AN: 31794

American (AMR) AF: 0.0000714 AC: 3 AN: 41992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23558

East Asian (EAS) AF: 0.00 AC: 0 AN: 38164

South Asian (SAS) AF: 0.00 AC: 0 AN: 78094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4046

European-Non Finnish (NFE) AF: 9.94e-7 AC: 1 AN: 1005876

Other (OTH) AF: 0.00 AC: 0 AN: 55694

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000507452), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000466 AC: 6 AN: 128754 Hom.: 0 Cov.: 20 AF XY: 0.0000483 AC XY: 3 AN XY: 62102

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

African (AFR) AF: 0.000165 AC: 6 AN: 36268

American (AMR) AF: 0.00 AC: 0 AN: 12824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2732

East Asian (EAS) AF: 0.00 AC: 0 AN: 4272

South Asian (SAS) AF: 0.00 AC: 0 AN: 3406

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57846

Other (OTH) AF: 0.00 AC: 0 AN: 1638

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00463839), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 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	0.080
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.7
DANN	Benign	0.84
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.056	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.50	N
PhyloP100		1.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.023
Sift	Benign	0.088	T
Sift4G	Benign	0.43	T
Polyphen		0.0010	B
Vest4		0.14
MVP		0.014
ClinPred		0.022	T
GERP RS		0.24
Varity_R		0.038
gMVP		0.28

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

Other links and lift over

dbSNP: rs1156764390; hg19: chr15-72954871;