15-34532868-A-C

Variant names:

• chr15-34532868-A-C
• rs1404148995
• NM_001023567.5:c.263T>G

Variant summary

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

The NM_001023567.5(GOLGA8B):​c.263T>G​(p.Leu88Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000812 in 1,107,886 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 20)
  • Exomes 𝑓: 0.0000081 (1 hom.)
• Consequence: GOLGA8B NM_001023567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.13

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8B	NM_001023567.5	c.263T>G	p.Leu88Arg	missense_variant	Exon 11 of 24	ENST00000683415.1	NP_001018861.3
GOLGA8B	NR_027410.2	n.2701T>G		non_coding_transcript_exon_variant	Exon 11 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA8B	ENST00000683415.1	c.263T>G	p.Leu88Arg	missense_variant	Exon 11 of 24		NM_001023567.5	ENSP00000507830.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD3 exomes AF: 0.00000511 AC: 1 AN: 195802 Hom.: 0 AF XY: 0.00000952 AC XY: 1 AN XY: 105060

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000721

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000812 AC: 9 AN: 1107886 Hom.: 1 Cov.: 22 AF XY: 0.00000361 AC XY: 2 AN XY: 553498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000282

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 20

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.263T>G (p.L88R) alteration is located in exon 3 (coding exon 3) of the GOLGA8B gene. This alteration results from a T to G substitution at nucleotide position 263, causing the leucine (L) at amino acid position 88 to be replaced by an arginine (R). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	0.16
Eigen_PC	Benign	-0.035
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-4.1	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.50		Loss of stability (P = 0.0147);.;
MVP		0.76
ClinPred		0.85	D
GERP RS		1.5
Varity_R		0.45
gMVP		0.59

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: rs1404148995; hg19: chr15-34825069;