chr15-34381823-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181077.5(GOLGA8A):c.1487C>G(p.Ala496Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A496V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000012 ( 0 hom., cov: 10)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8A
NM_181077.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.331

Publications

0 publications found

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:

MIR1233-1 (HGNC:33929): (microRNA 1233-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR1233-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06611395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8A	NM_181077.5 link	c.1487C>G	p.Ala496Gly	missense_variant	Exon 24 of 25	ENST00000359187.5	NP_851422.1	A7E2F4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GOLGA8A	ENST00000359187.5 link	c.1487C>G	p.Ala496Gly	missense_variant	Exon 24 of 25	1	NM_181077.5	ENSP00000352111.4	A7E2F4-3
GOLGA8A	ENST00000473125.5 link	n.3565C>G		non_coding_transcript_exon_variant	Exon 22 of 23	1
GOLGA8A	ENST00000699472.1 link	c.1484C>G	p.Ala495Gly	missense_variant	Exon 24 of 25			ENSP00000514395.1	A0A8V8TPN8
MIR1233-1	ENST00000408722.1 link	n.*246C>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000122

AC:

AN:

82236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000333

AC:

AN:

600766

Hom.:

Cov.:

AF XY:

0.00000642

AC XY:

AN XY:

311438

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:

19380

American (AMR)

AF:

0.00

AC:

AN:

28296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17016

East Asian (EAS)

AF:

0.00

AC:

AN:

31020

South Asian (SAS)

AF:

0.00

AC:

AN:

53400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2350

European-Non Finnish (NFE)

AF:

0.00000518

AC:

AN:

386260

Other (OTH)

AF:

0.00

AC:

AN:

31642

⚠️ 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: 0.250

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000122

AC:

AN:

82236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

38500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27036

American (AMR)

AF:

0.00

AC:

AN:

8358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2370

East Asian (EAS)

AF:

0.00

AC:

AN:

2134

South Asian (SAS)

AF:

0.00

AC:

AN:

2062

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

33654

Other (OTH)

AF:

0.00

AC:

AN:

1022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.37

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0098

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.066

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

L;.

PhyloP100

0.33

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.057

Sift

Benign

0.11

.;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0040

B;B

Vest4

0.13

MutPred

0.24

Loss of helix (P = 0.0626);.;

MVP

0.043

ClinPred

0.051

GERP RS

-0.60

Varity_R

0.023

gMVP

0.053

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over