15-34527934-C-G

Variant names:

• chr15-34527934-C-G
• rs202126811
• NM_001023567.5:c.1597G>C

Variant summary

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

The NM_001023567.5(GOLGA8B):​c.1597G>C​(p.Asp533His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D533N) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000084 (0 hom., cov: 19)
  • Exomes 𝑓: 0.0000086 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8B NM_001023567.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• 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=0.04795167).

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.1597G>C	p.Asp533His	missense	Exon 23 of 24	NP_001018861.3	A8MQT2-1
	GOLGA8B	NR_027410.2		n.4035G>C		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.1597G>C	p.Asp533His	missense	Exon 23 of 24	ENSP00000507830.1	A8MQT2-1
	GOLGA8B	ENST00000342314.9	TSL:1	c.1597G>C	p.Asp533His	missense	Exon 15 of 16	ENSP00000343064.5	A8MQT2-1
	GOLGA8B	ENST00000484716.5	TSL:1	n.3921G>C		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes AF: 0.00000842 AC: 1 AN: 118764 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00

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: 0.0000169

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000861 AC: 11 AN: 1277690 Hom.: 0 Cov.: 25 AF XY: 0.00000784 AC XY: 5 AN XY: 637568

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

African (AFR) AF: 0.00 AC: 0 AN: 24700

American (AMR) AF: 0.0000297 AC: 1 AN: 33616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21782

East Asian (EAS) AF: 0.00 AC: 0 AN: 37452

South Asian (SAS) AF: 0.00 AC: 0 AN: 75018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3748

European-Non Finnish (NFE) AF: 0.0000102 AC: 10 AN: 979218

Other (OTH) AF: 0.00 AC: 0 AN: 53168

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000417720), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000842 AC: 1 AN: 118764 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 57260

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

African (AFR) AF: 0.00 AC: 0 AN: 26214

American (AMR) AF: 0.00 AC: 0 AN: 11272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2606

East Asian (EAS) AF: 0.00 AC: 0 AN: 4474

South Asian (SAS) AF: 0.00 AC: 0 AN: 3470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8884

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

European-Non Finnish (NFE) AF: 0.0000169 AC: 1 AN: 59152

Other (OTH) AF: 0.00 AC: 0 AN: 1598

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.5
DANN	Benign	0.64
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0077	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.61	N
PhyloP100		-0.029
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.030
Sift	Benign	0.12	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.13
MutPred		0.22		Gain of methylation at K534 (P = 0.0542)
MVP		0.014
ClinPred		0.15	T
GERP RS		-0.73
Varity_R		0.041
gMVP		0.17
Mutation Taster		=99/1	polymorphism

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: rs202126811; hg19: chr15-34820135;