Genetic Variant GOLGA8B:p.Ser61Ala (chr15-34532950-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001023567.5(GOLGA8B):c.181T>G(p.Ser61Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 9)

Exomes 𝑓: 0.00022 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8B
NM_001023567.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Variant links:

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04371339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8B	NM_001023567.5 link	c.181T>G	p.Ser61Ala	missense_variant	Exon 11 of 24	ENST00000683415.1	NP_001018861.3	A8MQT2-1
GOLGA8B	NR_027410.2 link	n.2619T>G		non_coding_transcript_exon_variant	Exon 11 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA8B	ENST00000683415.1 link	c.181T>G	p.Ser61Ala	missense_variant	Exon 11 of 24		NM_001023567.5	ENSP00000507830.1		A8MQT2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

64422

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000584

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000169

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00101

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000327

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000200

AC:

AN:

130056

Hom.:

AF XY:

0.000219

AC XY:

AN XY:

68406

show subpopulations

Gnomad AFR exome

AF:

0.000860

Gnomad AMR exome

AF:

0.000124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000203

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000227

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000224

AC:

195

AN:

872400

Hom.:

Cov.:

AF XY:

0.000260

AC XY:

115

AN XY:

441760

show subpopulations

Gnomad4 AFR exome

AF:

0.00144

Gnomad4 AMR exome

AF:

0.0000775

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000128

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.0000715

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000468

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000387

AC:

AN:

64532

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

30666

show subpopulations

Gnomad4 AFR

AF:

0.000582

Gnomad4 AMR

AF:

0.000169

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00101

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000327

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000590

Hom.:

ExAC

AF:

0.000243

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.181T>G (p.S61A) alteration is located in exon 3 (coding exon 3) of the GOLGA8B gene. This alteration results from a T to G substitution at nucleotide position 181, causing the serine (S) at amino acid position 61 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.049

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.24

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.086

Sift

Uncertain

0.012

D;T

Sift4G

Uncertain

0.029

D;D

Polyphen

0.90

P;.

Vest4

0.25

MVP

0.048

ClinPred

0.054

GERP RS

1.3

Varity_R

0.16

gMVP

0.052

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over