Genetic Variant GOLGA8B:p.His505Tyr (chr15-34528018-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001023567.5(GOLGA8B):c.1513C>T(p.His505Tyr) 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00010 ( 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: 1.42

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.041078).

BP6

Variant 15-34528018-G-A is Benign according to our data. Variant chr15-34528018-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2377833.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8B	NM_001023567.5 link	c.1513C>T	p.His505Tyr	missense_variant	Exon 23 of 24	ENST00000683415.1	NP_001018861.3	A8MQT2-1
GOLGA8B	NR_027410.2 link	n.3951C>T		non_coding_transcript_exon_variant	Exon 23 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA8B	ENST00000683415.1 link	c.1513C>T	p.His505Tyr	missense_variant	Exon 23 of 24		NM_001023567.5	ENSP00000507830.1		A8MQT2-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

63330

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000979

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00589

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000814

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000101

AC:

AN:

793612

Hom.:

Cov.:

AF XY:

0.000103

AC XY:

AN XY:

406256

show subpopulations

Gnomad4 AFR exome

AF:

0.0000672

Gnomad4 AMR exome

AF:

0.0000777

Gnomad4 ASJ exome

AF:

0.00395

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000875

Gnomad4 OTH exome

AF:

0.000273

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000205

AC:

AN:

63360

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

29898

show subpopulations

Gnomad4 AFR

AF:

0.0000977

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00589

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000814

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 18, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.11

Sift

Benign

0.13

T;T

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.11

MutPred

0.34

Gain of phosphorylation at H505 (P = 0.0535);.;

MVP

0.030

ClinPred

0.20

GERP RS

-2.1

Varity_R

0.24

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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