15-34381524-G-C

Position:

• chr15-34381524-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181077.5(GOLGA8A):​c.1699C>G​(p.Pro567Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,556 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000082 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8A NM_181077.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.17

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17530653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GOLGA8A	NM_181077.5	c.1699C>G	p.Pro567Ala	missense_variant	25/25	ENST00000359187.5	NP_851422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GOLGA8A	ENST00000359187.5	c.1699C>G	p.Pro567Ala	missense_variant	25/25	1	NM_181077.5	ENSP00000352111.4
GOLGA8A	ENST00000473125.5	n.3777C>G		non_coding_transcript_exon_variant	23/23	1
GOLGA8A	ENST00000699472.1	c.1696C>G	p.Pro566Ala	missense_variant	25/25			ENSP00000514395.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151556 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251454 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000821 AC: 12 AN: 1461034 Hom.: 0 Cov.: 38 AF XY: 0.00000963 AC XY: 7 AN XY: 726834

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000720

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151556 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 73968

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

The c.1699C>G (p.P567A) alteration is located in exon 16 (coding exon 16) of the GOLGA8A gene. This alteration results from a C to G substitution at nucleotide position 1699, causing the proline (P) at amino acid position 567 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.1	.;D
REVEL	Benign	0.085
Sift	Benign	0.11	.;T
Sift4G	Uncertain	0.060	T;T
Polyphen		0.80	P;D
Vest4		0.11
MutPred		0.41		Loss of disorder (P = 0.0597);.;
MVP		0.043
ClinPred		0.33	T
GERP RS		0.51
Varity_R		0.044
gMVP		0.056

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: rs772090115; hg19: chr15-34673725;