rs347881

chr15-34382108-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_181077.5(GOLGA8A):c.1353-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (16 hom., cov: 0)
  • Exomes 𝑓: 0.72 (38856 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA8A NM_181077.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

Genes affected

GOLGA8A (HGNC:31972): (golgin A8 family member A) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked, flattened membrane sacs referred to as cisternae. Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. The golgins constitute a family of proteins which are localized to the Golgi. This gene encodes a golgin which structurally resembles its family member GOLGA2, suggesting that they may share a similar function. There are many similar copies of this gene on chromosome 15. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2009]

MIR1233-1 (HGNC:33929): (microRNA 1233-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BS2: High Homozygotes in GnomAdExome at 6158 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA8A	NM_181077.5	c.1353-40A>G		intron_variant		ENST00000359187.5
MIR1233-1	NR_036050.1	n.43A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA8A	ENST00000359187.5	c.1353-40A>G		intron_variant		1	NM_181077.5	P4
MIR1233-1	ENST00000408722.1	n.43A>G		non_coding_transcript_exon_variant	1/1
GOLGA8A	ENST00000473125.5	n.3431-40A>G		intron_variant, non_coding_transcript_variant		1
GOLGA8A	ENST00000699472.1	c.1350-40A>G		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 50 AN: 74 Hom.: 16 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.500

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.500

Gnomad NFE AF: 0.750

Gnomad OTH AF: 1.00

GnomAD3 exomes AF: 0.703 AC: 20748 AN: 29524 Hom.: 6158 AF XY: 0.704 AC XY: 10688 AN XY: 15176

Gnomad AFR exome AF: 0.566

Gnomad AMR exome AF: 0.776

Gnomad ASJ exome AF: 0.736

Gnomad EAS exome AF: 0.742

Gnomad SAS exome AF: 0.807

Gnomad FIN exome AF: 0.702

Gnomad NFE exome AF: 0.666

Gnomad OTH exome AF: 0.719

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.718 AC: 125825 AN: 175190 Hom.: 38856 Cov.: 0 AF XY: 0.728 AC XY: 66907 AN XY: 91926

Gnomad4 AFR exome AF: 0.575

Gnomad4 AMR exome AF: 0.794

Gnomad4 ASJ exome AF: 0.754

Gnomad4 EAS exome AF: 0.767

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.741

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.718

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.676 AC: 50 AN: 74 Hom.: 16 Cov.: 0 AF XY: 0.719 AC XY: 23 AN XY: 32

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 1.00

Alfa AF: 0.806 Hom.: 3769

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	3.7
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs347881; hg19: chr15-34674309;