15-34527778-C-G

Variant names:

• chr15-34527778-C-G
• rs753342353
• NM_001023567.5:c.1666G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001023567.5(GOLGA8B):​c.1666G>C​(p.Glu556Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,465,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E556D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: GOLGA8B NM_001023567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.782
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10978103).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8B	NM_001023567.5	MANE Select	c.1666G>C	p.Glu556Gln	missense	Exon 24 of 24	NP_001018861.3	A8MQT2-1
	GOLGA8B	NR_027410.2		n.4104G>C		non_coding_transcript_exon	Exon 24 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8B	ENST00000683415.1	MANE Select	c.1666G>C	p.Glu556Gln	missense	Exon 24 of 24	ENSP00000507830.1	A8MQT2-1
	GOLGA8B	ENST00000342314.9	TSL:1	c.1666G>C	p.Glu556Gln	missense	Exon 16 of 16	ENSP00000343064.5	A8MQT2-1
	GOLGA8B	ENST00000484716.5	TSL:1	n.3990G>C		non_coding_transcript_exon	Exon 23 of 23

Frequencies

GnomAD3 genomes AF: 0.0000166 AC: 2 AN: 120474 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000358

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: 0.0000168

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000143 AC: 3 AN: 209208 AF XY: 0.0000176

Gnomad AFR exome AF: 0.0000871

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000206

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000149 AC: 2 AN: 1344964 Hom.: 0 Cov.: 31 AF XY: 0.00000298 AC XY: 2 AN XY: 671084

African (AFR) AF: 0.00 AC: 0 AN: 27136

American (AMR) AF: 0.00 AC: 0 AN: 36138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22918

East Asian (EAS) AF: 0.00 AC: 0 AN: 38240

South Asian (SAS) AF: 0.00 AC: 0 AN: 79002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4388

European-Non Finnish (NFE) AF: 9.71e-7 AC: 1 AN: 1029934

Other (OTH) AF: 0.0000180 AC: 1 AN: 55652

GnomAD4 genome AF: 0.0000166 AC: 2 AN: 120474 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 58268

African (AFR) AF: 0.0000358 AC: 1 AN: 27938

American (AMR) AF: 0.00 AC: 0 AN: 10962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2608

East Asian (EAS) AF: 0.00 AC: 0 AN: 4486

South Asian (SAS) AF: 0.00 AC: 0 AN: 3588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 258

European-Non Finnish (NFE) AF: 0.0000168 AC: 1 AN: 59688

Other (OTH) AF: 0.00 AC: 0 AN: 1620

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.0000173 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.78
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.049
Sift	Benign	0.16	T
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.053
MutPred		0.18		Loss of phosphorylation at S559 (P = 0.1781)
MVP		0.030
ClinPred		0.17	T
GERP RS		-3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083
gMVP		0.062

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

Other links and lift over

dbSNP: rs753342353; hg19: chr15-34819979;