rs9644946

chr9-124923227-T-Cchr9-124923227-T-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002077.4(GOLGA1):c.433-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0159 in 1,585,686 control chromosomes in the GnomAD database, including 1,302 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (123 hom., cov: 32)
  • Exomes 𝑓: 0.016 (1179 hom.)
• Consequence: GOLGA1 NM_002077.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.9870
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

Genes affected

GOLGA1 (HGNC:4424): (golgin A1) The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. This gene encodes one of the golgins, a family of proteins localized to the Golgi. This encoded protein is associated with Sjogren's syndrome. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA1	NM_002077.4	c.433-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000373555.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA1	ENST00000373555.9	c.433-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002077.4	P1
GOLGA1	ENST00000475407.5	c.185-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2437 AN: 152224 Hom.: 123 Cov.: 32

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00469

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.0332 AC: 8028 AN: 241488 Hom.: 446 AF XY: 0.0368 AC XY: 4811 AN XY: 130732

Gnomad AFR exome AF: 0.000499

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.160

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0524

Gnomad NFE exome AF: 0.00552

Gnomad OTH exome AF: 0.0236

GnomAD4 exome AF: 0.0159 AC: 22768 AN: 1433344 Hom.: 1179 Cov.: 25 AF XY: 0.0187 AC XY: 13371 AN XY: 714414

Gnomad4 AFR exome AF: 0.00107

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.0267

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0504

Gnomad4 NFE exome AF: 0.00319

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0160 AC: 2437 AN: 152342 Hom.: 123 Cov.: 32 AF XY: 0.0208 AC XY: 1546 AN XY: 74488

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.00469

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00722 Hom.: 4

Bravo AF: 0.0109

Asia WGS AF: 0.100 AC: 347 AN: 3478

EpiCase AF: 0.00415

EpiControl AF: 0.00457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	22
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.79
SpliceAI score (max)		0.95		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.95		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9644946; hg19: chr9-127685506;