chr15-34527931-T-C

Variant names:

• chr15-34527931-T-C
• rs767416468
• NM_001023567.5:c.1600A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001023567.5(GOLGA8B):​c.1600A>G​(p.Lys534Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (1 hom., cov: 19)
  • Exomes 𝑓: 0.00010 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8B NM_001023567.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0340
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048156977).

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.1600A>G	p.Lys534Glu	missense	Exon 23 of 24	NP_001018861.3	A8MQT2-1
	GOLGA8B	NR_027410.2		n.4038A>G		non_coding_transcript_exon	Exon 23 of 24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA8B	ENST00000683415.1	MANE Select	c.1600A>G	p.Lys534Glu	missense	Exon 23 of 24	ENSP00000507830.1	A8MQT2-1
	GOLGA8B	ENST00000342314.9	TSL:1	c.1600A>G	p.Lys534Glu	missense	Exon 15 of 16	ENSP00000343064.5	A8MQT2-1
	GOLGA8B	ENST00000484716.5	TSL:1	n.3924A>G		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes AF: 0.000215 AC: 26 AN: 121066 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

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: 0.000117

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000278 AC: 33 AN: 118702 AF XY: 0.000251

Gnomad AFR exome AF: 0.000331

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.000591

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000104 AC: 133 AN: 1281494 Hom.: 5 Cov.: 25 AF XY: 0.000111 AC XY: 71 AN XY: 639538

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000161 AC: 4 AN: 24774

American (AMR) AF: 0.00112 AC: 38 AN: 33918

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21876

East Asian (EAS) AF: 0.00 AC: 0 AN: 37574

South Asian (SAS) AF: 0.00 AC: 0 AN: 75340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3792

European-Non Finnish (NFE) AF: 0.0000825 AC: 81 AN: 981506

Other (OTH) AF: 0.000187 AC: 10 AN: 53360

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000770495), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000215 AC: 26 AN: 121096 Hom.: 1 Cov.: 19 AF XY: 0.000239 AC XY: 14 AN XY: 58564

African (AFR) AF: 0.000148 AC: 4 AN: 27074

American (AMR) AF: 0.00130 AC: 15 AN: 11522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 4524

South Asian (SAS) AF: 0.00 AC: 0 AN: 3570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.000117 AC: 7 AN: 59994

Other (OTH) AF: 0.00 AC: 0 AN: 1656

Alfa AF: 0.000132 Hom.: 0

ExAC AF: 0.0000513 AC: 5

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	-0.60	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.88
DANN	Benign	0.48
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.034
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.018
Sift	Benign	0.82	T
Sift4G	Benign	0.55	T
Polyphen		0.99	D
Vest4		0.059
MutPred		0.23		Loss of ubiquitination at K534 (P = 3e-04)
MVP		0.014
ClinPred		0.0061	T
GERP RS		-2.9
Varity_R		0.070
gMVP		0.058
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs767416468; hg19: chr15-34820132;