Genetic Variant GOLGA6B:p.Glu334Lys (chr15-72662404-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018652.5(GOLGA6B):c.1000G>A(p.Glu334Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000536 in 1,396,554 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 15 hom., cov: 20)

Exomes 𝑓: 0.00055 ( 193 hom. )

Consequence

GOLGA6B
NM_018652.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.87

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071727633).

BS2

High Homozygotes in GnomAd4 at 15 AR gene

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.1000G>A	p.Glu334Lys	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.1000G>A	p.Glu334Lys	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.994G>A	p.Glu332Lys	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes

AF:

0.000403

AC:

AN:

126652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000833

Gnomad AMI

AF:

0.0182

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:

0.000631

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000365

AC:

AN:

216528

AF XY:

0.000359

show subpopulations

Gnomad AFR exome

AF:

0.000143

Gnomad AMR exome

AF:

0.000255

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000650

Gnomad OTH exome

AF:

0.000748

GnomAD4 exome

AF:

0.000549

AC:

697

AN:

1269786

Hom.:

193

Cov.:

AF XY:

0.000551

AC XY:

347

AN XY:

629466

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

31092

American (AMR)

AF:

0.000175

AC:

AN:

39916

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20906

East Asian (EAS)

AF:

0.00

AC:

AN:

33814

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69464

European-Finnish (FIN)

AF:

0.0000438

AC:

AN:

45712

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4420

European-Non Finnish (NFE)

AF:

0.000684

AC:

665

AN:

972116

Other (OTH)

AF:

0.000306

AC:

AN:

52346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000402

AC:

AN:

126768

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

AN XY:

61186

show subpopulations

African (AFR)

AF:

0.0000831

AC:

AN:

36122

American (AMR)

AF:

0.00

AC:

AN:

12666

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

4088

South Asian (SAS)

AF:

0.00

AC:

AN:

3356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

56998

Other (OTH)

AF:

0.00

AC:

AN:

1650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000352

Hom.:

ExAC

AF:

0.000274

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.8

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.32

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0072

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.2

REVEL

Benign

0.081

Sift

Benign

0.21

Sift4G

Benign

0.29

Polyphen

0.16

Vest4

0.19

MVP

0.055

ClinPred

0.045

GERP RS

-0.74

Varity_R

0.046

gMVP

0.49

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over