Genetic Variant GOLGA8B:p.Asp533Asn (chr15-34527934-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001023567.5(GOLGA8B):c.1597G>A(p.Asp533Asn) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8B
NM_001023567.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0290

Publications

0 publications found

Variant links:

COSMIC-nc: COSV50989163

Genes affected

GOLGA8B (HGNC:31973): (golgin A8 family member B) Predicted to be involved in Golgi organization and spindle assembly. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

GOLGA8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013385445).

BP6

Variant 15-34527934-C-T is Benign according to our data. Variant chr15-34527934-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2590579.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023567.5. 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
	GOLGA8B	NM_001023567.5	MANE Select	c.1597G>A	p.Asp533Asn	missense	Exon 23 of 24	NP_001018861.3	A8MQT2-1
	GOLGA8B	NR_027410.2		n.4035G>A		non_coding_transcript_exon	Exon 23 of 24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLGA8B	ENST00000683415.1	MANE Select	c.1597G>A	p.Asp533Asn	missense	Exon 23 of 24	ENSP00000507830.1	A8MQT2-1
GOLGA8B	ENST00000342314.9	TSL:1	c.1597G>A	p.Asp533Asn	missense	Exon 15 of 16	ENSP00000343064.5	A8MQT2-1
GOLGA8B	ENST00000484716.5	TSL:1	n.3921G>A		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes

AF:

0.0000589

AC:

AN:

118760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000763

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:

0.0000845

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000132

AC:

AN:

113824

AF XY:

0.0000817

show subpopulations

Gnomad AFR exome

AF:

0.000170

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000190

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000131

AC:

167

AN:

1277594

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

637538

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

24698

American (AMR)

AF:

0.00

AC:

AN:

33616

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21782

East Asian (EAS)

AF:

0.0000534

AC:

AN:

37448

South Asian (SAS)

AF:

0.000160

AC:

AN:

75018

European-Finnish (FIN)

AF:

0.0000204

AC:

AN:

48986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3748

European-Non Finnish (NFE)

AF:

0.000151

AC:

148

AN:

979130

Other (OTH)

AF:

0.0000752

AC:

AN:

53168

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.330

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000589

AC:

AN:

118760

Hom.:

Cov.:

AF XY:

0.0000349

AC XY:

AN XY:

57258

show subpopulations

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

African (AFR)

AF:

0.0000763

AC:

AN:

26212

American (AMR)

AF:

0.00

AC:

AN:

11272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2606

East Asian (EAS)

AF:

0.00

AC:

AN:

4474

South Asian (SAS)

AF:

0.00

AC:

AN:

3470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8884

Middle Eastern (MID)

AF:

0.00

AC:

AN:

258

European-Non Finnish (NFE)

AF:

0.0000845

AC:

AN:

59150

Other (OTH)

AF:

0.00

AC:

AN:

1598

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000116185), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.354

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000942

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.086

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.5

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.31

M_CAP

Benign

0.0012

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.48

PhyloP100

-0.029

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.66

REVEL

Benign

0.041

Sift

Benign

0.37

Sift4G

Benign

0.62

Polyphen

1.0

Vest4

0.12

MutPred

0.22

Gain of methylation at K534 (P = 0.0599)

MVP

0.014

ClinPred

0.014

GERP RS

-0.73

Varity_R

0.033

gMVP

0.090

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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