chr15-34381601-G-A

Position:

chr15-34381601-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_181077.5(GOLGA8A):c.1622C>T(p.Ala541Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 136,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8A
NM_181077.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.03

Variant links:

Genes affected

GOLGA8A (HGNC:31972): (golgin A8 family member A) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked, flattened membrane sacs referred to as cisternae. Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. The golgins constitute a family of proteins which are localized to the Golgi. This gene encodes a golgin which structurally resembles its family member GOLGA2, suggesting that they may share a similar function. There are many similar copies of this gene on chromosome 15. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

GOLGA8A links:

GOLGA8A (HGNC:):

GOLGA8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01501745).

BP6

Variant 15-34381601-G-A is Benign according to our data. Variant chr15-34381601-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3281923.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA8A	NM_181077.5 linkuse as main transcript	c.1622C>T	p.Ala541Val	missense_variant	25/25	ENST00000359187.5	NP_851422.1	A7E2F4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GOLGA8A	ENST00000359187.5 linkuse as main transcript	c.1622C>T	p.Ala541Val	missense_variant	25/25	1	NM_181077.5	ENSP00000352111.4	A7E2F4-3
GOLGA8A	ENST00000473125.5 linkuse as main transcript	n.3700C>T		non_coding_transcript_exon_variant	23/23	1
GOLGA8A	ENST00000699472.1 linkuse as main transcript	c.1619C>T	p.Ala540Val	missense_variant	25/25			ENSP00000514395.1	A0A8V8TPN8

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

136598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000878

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:

0.000544

GnomAD3 exomes

AF:

0.0000142

AC:

AN:

211892

Hom.:

AF XY:

0.0000177

AC XY:

AN XY:

113012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000701

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000109

Gnomad OTH exome

AF:

0.000185

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000107

AC:

AN:

1307892

Hom.:

Cov.:

AF XY:

0.00000919

AC XY:

AN XY:

652916

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000706

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000270

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000511

Gnomad4 OTH exome

AF:

0.0000904

GnomAD4 genome

AF:

0.000117

AC:

AN:

136598

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

66146

show subpopulations

Gnomad4 AFR

AF:

0.0000748

Gnomad4 AMR

AF:

0.000878

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000544

Alfa

AF:

0.0000480

Hom.:

ExAC

AF:

0.0000184

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

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

0.051

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.8

DANN

Benign

0.73

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0027

LIST_S2

Benign

0.54

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.8

N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

2.7

.;N

REVEL

Benign

0.041

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.075

MutPred

0.16

Gain of catalytic residue at A569 (P = 0.0531);.;

MVP

0.043

ClinPred

0.012

GERP RS

0.51

Varity_R

0.037

gMVP

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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