15-34528054-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001023567.5(GOLGA8B):c.1477G>A(p.Asp493Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., cov: 8)

Exomes 𝑓: 0.0022 ( 87 hom. )

Failed GnomAD Quality Control

Consequence

GOLGA8B
NM_001023567.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.172

Publications

2 publications found

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:

MIR1233-2 (HGNC:38277): (microRNA 1233-2) 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]

MIR1233-2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007884711).

BP6

Variant 15-34528054-C-T is Benign according to our data. Variant chr15-34528054-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2345549.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001023567.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLGA8B	NM_001023567.5	MANE Select	c.1477G>A	p.Asp493Asn	missense	Exon 23 of 24	NP_001018861.3	A8MQT2-1
GOLGA8B	NR_027410.2		n.3915G>A		non_coding_transcript_exon	Exon 23 of 24
MIR1233-2	NR_036261.1		n.*236G>A		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GOLGA8B	ENST00000683415.1	MANE Select	c.1477G>A	p.Asp493Asn	missense	Exon 23 of 24	ENSP00000507830.1	A8MQT2-1
GOLGA8B	ENST00000342314.9	TSL:1	c.1477G>A	p.Asp493Asn	missense	Exon 15 of 16	ENSP00000343064.5	A8MQT2-1
GOLGA8B	ENST00000484716.5	TSL:1	n.3801G>A		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes

AF:

0.000573

AC:

AN:

64540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000372

Gnomad ASJ

AF:

0.0146

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000639

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000241

Gnomad OTH

AF:

0.00405

GnomAD2 exomes

AF:

0.0108

AC:

535

AN:

49634

AF XY:

0.0111

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.0333

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.00289

Gnomad FIN exome

AF:

0.00252

Gnomad NFE exome

AF:

0.00155

Gnomad OTH exome

AF:

0.0110

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00224

AC:

1374

AN:

614728

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

727

AN XY:

319638

show subpopulations

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

African (AFR)

AF:

0.00266

AC:

AN:

12412

American (AMR)

AF:

0.0155

AC:

352

AN:

22722

Ashkenazi Jewish (ASJ)

AF:

0.0232

AC:

319

AN:

13748

East Asian (EAS)

AF:

0.000803

AC:

AN:

31148

South Asian (SAS)

AF:

0.00283

AC:

147

AN:

51902

European-Finnish (FIN)

AF:

0.000917

AC:

AN:

30530

Middle Eastern (MID)

AF:

0.00317

AC:

AN:

2210

European-Non Finnish (NFE)

AF:

0.000896

AC:

376

AN:

419442

Other (OTH)

AF:

0.00284

AC:

AN:

30614

⚠️ 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: 0.352

Heterozygous variant carriers

143

214

286

357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.000573

AC:

AN:

64572

Hom.:

Cov.:

AF XY:

0.000558

AC XY:

AN XY:

30456

show subpopulations

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

African (AFR)

AF:

0.000101

AC:

AN:

9948

American (AMR)

AF:

0.000371

AC:

AN:

5384

Ashkenazi Jewish (ASJ)

AF:

0.0146

AC:

AN:

1436

East Asian (EAS)

AF:

0.00

AC:

AN:

2656

South Asian (SAS)

AF:

0.000637

AC:

AN:

1570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

140

European-Non Finnish (NFE)

AF:

0.000241

AC:

AN:

37400

Other (OTH)

AF:

0.00401

AC:

AN:

748

⚠️ 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: 0.331

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00988

Hom.:

ExAC

AF:

0.000508

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.032

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0079

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

PhyloP100

-0.17

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.058

Sift

Uncertain

0.020

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.11

MutPred

0.27

Loss of helix (P = 0.1706)

ClinPred

0.039

GERP RS

-2.1

Varity_R

0.089

gMVP

0.099

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over