Genetic Variant GOLGA6B:p.Ala327Thr (chr15-72662383-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.979G>A(p.Ala327Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000481 in 1,392,590 control chromosomes in the GnomAD database, including 14 homozygotes. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A327D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00016 ( 3 hom., cov: 20)

Exomes 𝑓: 0.000037 ( 11 hom. )

Consequence

GOLGA6B
NM_018652.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.259

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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.047303468).

BS2

High Homozygotes in GnomAd4 at 3 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.979G>A	p.Ala327Thr	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.979G>A	p.Ala327Thr	missense	Exon 11 of 18	ENSP00000408132.3	A6NDN3
	GOLGA6B	ENST00000909077.1		c.973G>A	p.Ala325Thr	missense	Exon 11 of 18	ENSP00000579136.1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

126522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000527

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000790

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:

0.0000784

AC:

AN:

216714

AF XY:

0.0000598

show subpopulations

Gnomad AFR exome

AF:

0.000491

Gnomad AMR exome

AF:

0.0000958

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.000562

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1266068

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

627638

show subpopulations

African (AFR)

AF:

0.000322

AC:

AN:

31064

American (AMR)

AF:

0.000151

AC:

AN:

39864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20880

East Asian (EAS)

AF:

0.00

AC:

AN:

33840

South Asian (SAS)

AF:

0.0000291

AC:

AN:

68818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45648

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4290

European-Non Finnish (NFE)

AF:

0.0000248

AC:

AN:

969480

Other (OTH)

AF:

0.0000958

AC:

AN:

52184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000158

AC:

AN:

126522

Hom.:

Cov.:

AF XY:

0.0000984

AC XY:

AN XY:

60978

show subpopulations

African (AFR)

AF:

0.000527

AC:

AN:

36042

American (AMR)

AF:

0.0000790

AC:

AN:

12656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.00

AC:

AN:

4096

South Asian (SAS)

AF:

0.00

AC:

AN:

3324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8342

Middle Eastern (MID)

AF:

0.00

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56882

Other (OTH)

AF:

0.00

AC:

AN:

1608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

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:

0.00

Hom.:

ExAC

AF:

0.0000625

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

0.097

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.6

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0023

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.0065

LIST_S2

Benign

0.15

M_CAP

Benign

0.0020

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.26

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.85

REVEL

Benign

0.018

Sift

Benign

0.67

Sift4G

Benign

0.63

Polyphen

0.99

Vest4

0.060

MVP

0.040

ClinPred

0.015

GERP RS

0.37

Varity_R

0.029

gMVP

0.049

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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