rs1275378091

Variant names:

Your query was ambiguous. Multiple possible variants found:

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>T(p.Ala496Val) 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 10)

Exomes 𝑓: 0.000035 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8A
NM_181077.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.032642007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8A	NM_181077.5 link	c.1487C>T	p.Ala496Val	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>T	p.Ala496Val	missense_variant	Exon 24 of 25	1	NM_181077.5	ENSP00000352111.4	A7E2F4-3
GOLGA8A	ENST00000473125.5 link	n.3565C>T		non_coding_transcript_exon_variant	Exon 22 of 23	1
GOLGA8A	ENST00000699472.1 link	c.1484C>T	p.Ala495Val	missense_variant	Exon 24 of 25			ENSP00000514395.1	A0A8V8TPN8
MIR1233-1	ENST00000408722.1 link	n.*246C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.000231

AC:

AN:

82230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000703

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000113

AC:

AN:

62198

AF XY:

0.000127

show subpopulations

Gnomad AFR exome

AF:

0.000887

Gnomad AMR exome

AF:

0.0000735

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000350

AC:

AN:

600762

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

311438

show subpopulations

African (AFR)

AF:

0.000516

AC:

AN:

19380

American (AMR)

AF:

0.0000707

AC:

AN:

28294

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:

0.0000233

AC:

AN:

386258

Other (OTH)

AF:

0.00

AC:

AN:

31642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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:

0.000231

AC:

AN:

82230

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

38498

show subpopulations

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

African (AFR)

AF:

0.000703

AC:

AN:

27030

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:

0.00

AC:

AN:

33654

Other (OTH)

AF:

0.00

AC:

AN:

1022

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.336

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:

0.0000638

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1487C>T (p.A496V) alteration is located in exon 15 (coding exon 15) of the GOLGA8A gene. This alteration results from a C to T substitution at nucleotide position 1487, causing the alanine (A) at amino acid position 496 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.28

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0030

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.2

L;.

PhyloP100

0.33

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.037

Sift

Benign

0.29

.;T

Sift4G

Benign

0.60

T;T

Polyphen

0.11

B;P

Vest4

0.096

MutPred

0.38

Gain of sheet (P = 0.0028);.;

MVP

0.043

ClinPred

0.0049

GERP RS

-0.60

Varity_R

0.017

gMVP

0.052

Mutation Taster

=97/3

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over