chr15-32446531-C-A

Variant names:

• chr15-32446531-C-A
• rs772846509
• NM_001277308.1:c.1311G>T

Variant summary

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

The NM_001277308.1(GOLGA8O):​c.1311G>T​(p.Glu437Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E437E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 19)
• Consequence: GOLGA8O NM_001277308.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 0 publications found

Genes affected

GOLGA8O (HGNC:44406): (golgin A8 family member O) Predicted to be involved in Golgi organization. Predicted to be located in Golgi apparatus. Predicted to be active in Golgi cis cisterna; Golgi cisterna membrane; and cis-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

RN7SL539P (HGNC:46555): (RNA, 7SL, cytoplasmic 539, pseudogene)

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=0.13022846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277308.1. 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
	GOLGA8O	NM_001277308.1	MANE Select	c.1311G>T	p.Glu437Asp	missense	Exon 15 of 19	NP_001264237.1	A6NCC3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8O	ENST00000509311.7	TSL:5 MANE Select	c.1311G>T	p.Glu437Asp	missense	Exon 15 of 19	ENSP00000423159.2	A6NCC3-2
	RN7SL539P	ENST00000610974.1	TSL:6	n.*143G>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 19

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		-0.35
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.28	T
Sift4G	Uncertain	0.0040	D
Vest4		0.14
MutPred		0.062		Gain of relative solvent accessibility (P = 0.1894)
MVP		0.048
ClinPred		0.22	T
GERP RS		0.67
Varity_R		0.066
gMVP		0.10

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

Other links and lift over

dbSNP: rs772846509; hg19: chr15-32738732;