chr15-34382019-A-C

Position:

• chr15-34382019-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_181077.5(GOLGA8A):​c.1402T>G​(p.Ser468Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.25 (16 hom., cov: 1)
  • Exomes 𝑓: 0.17 (1107 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8A NM_181077.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.664

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014832914).
• BP6: Variant 15-34382019-A-C is Benign according to our data. Variant chr15-34382019-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2391094.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	c.1402T>G	p.Ser468Ala	missense_variant	23/25	ENST00000359187.5	NP_851422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA8A	ENST00000359187.5	c.1402T>G	p.Ser468Ala	missense_variant	23/25	1	NM_181077.5	ENSP00000352111.4
GOLGA8A	ENST00000473125.5	n.3480T>G		non_coding_transcript_exon_variant	21/23	1
GOLGA8A	ENST00000699472.1	c.1399T>G	p.Ser467Ala	missense_variant	23/25			ENSP00000514395.1
MIR1233-1	ENST00000408722.1	n.*50T>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 906 AN: 3636 Hom.: 15 Cov.: 1 FAILED QC

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.293

GnomAD3 exomes AF: 0.180 AC: 7196 AN: 40068 Hom.: 100 AF XY: 0.174 AC XY: 3540 AN XY: 20366

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.223

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.161

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.167 AC: 53813 AN: 321812 Hom.: 1107 Cov.: 0 AF XY: 0.170 AC XY: 28723 AN XY: 168984

Gnomad4 AFR exome AF: 0.247

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.223

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.250 AC: 909 AN: 3640 Hom.: 16 Cov.: 1 AF XY: 0.243 AC XY: 412 AN XY: 1698

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.291

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.293

Alfa AF: 0.141 Hom.: 103

ExAC AF: 0.0895 AC: 17

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

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	0.045
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.42
DEOGEN2	Benign	0.0011	T;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0015	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-3.1	N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	1.6	.;N
REVEL	Benign	0.023
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.027
ClinPred		0.0050	T
GERP RS		0.50
Varity_R		0.035
gMVP		0.057

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs781575400; hg19: chr15-34674220; COSMIC: COSV62169151; COSMIC: COSV62169151;