15-34527955-G-A

Variant names:

• chr15-34527955-G-A
• NM_001023567.5:c.1576C>T

Variant summary

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

The NM_001023567.5(GOLGA8B):​c.1576C>T​(p.Pro526Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 17)
• Consequence: GOLGA8B NM_001023567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.242

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15602425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA8B	NM_001023567.5	c.1576C>T	p.Pro526Ser	missense_variant	Exon 23 of 24	ENST00000683415.1	NP_001018861.3
GOLGA8B	NR_027410.2	n.4014C>T		non_coding_transcript_exon_variant	Exon 23 of 24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA8B	ENST00000683415.1	c.1576C>T	p.Pro526Ser	missense_variant	Exon 23 of 24		NM_001023567.5	ENSP00000507830.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 17

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1576C>T (p.P526S) alteration is located in exon 15 (coding exon 15) of the GOLGA8B gene. This alteration results from a C to T substitution at nucleotide position 1576, causing the proline (P) at amino acid position 526 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Benign	0.058
Sift	Benign	0.14	T;T
Sift4G	Uncertain	0.029	D;D
Polyphen		0.92	P;.
Vest4		0.070
MutPred		0.25		Loss of catalytic residue at P526 (P = 0.0226);.;
MVP		0.048
ClinPred		0.89	D
GERP RS		-2.6
Varity_R		0.15
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-34820156;