rs9644946

Variant names:

• chr9-124923227-T-C
• rs9644946
• NM_002077.4:c.433-4A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-124923227-T-C
• chr9-124923227-T-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_002077.4(GOLGA1):​c.433-4A>G variant causes a splice region, 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, intron
• Scores: Splicing: ADA: 0.9870
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• 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 rank	MANE	Protein	UniProt
GOLGA1	NM_002077.4	c.433-4A>G		splice_region_variant, intron_variant	Intron 7 of 22	ENST00000373555.9	NP_002068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA1	ENST00000373555.9	c.433-4A>G		splice_region_variant, intron_variant	Intron 7 of 22	1	NM_002077.4	ENSP00000362656.4
GOLGA1	ENST00000475407.5	n.184-4A>G		splice_region_variant, intron_variant	Intron 3 of 17	5		ENSP00000473648.1

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

GnomAD2 exomes AF: 0.0332 AC: 8028 AN: 241488 AF XY: 0.0368

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 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

African (AFR) AF: 0.00107 AC: 35 AN: 32740

American (AMR) AF: 0.00319 AC: 133 AN: 41690

Ashkenazi Jewish (ASJ) AF: 0.0267 AC: 689 AN: 25810

East Asian (EAS) AF: 0.151 AC: 5945 AN: 39304

South Asian (SAS) AF: 0.103 AC: 8541 AN: 83088

European-Finnish (FIN) AF: 0.0504 AC: 2663 AN: 52798

Middle Eastern (MID) AF: 0.0214 AC: 122 AN: 5700

European-Non Finnish (NFE) AF: 0.00319 AC: 3483 AN: 1092828

Other (OTH) AF: 0.0195 AC: 1157 AN: 59386

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

African (AFR) AF: 0.000649 AC: 27 AN: 41596

American (AMR) AF: 0.00340 AC: 52 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0277 AC: 96 AN: 3468

East Asian (EAS) AF: 0.155 AC: 802 AN: 5186

South Asian (SAS) AF: 0.114 AC: 552 AN: 4828

European-Finnish (FIN) AF: 0.0531 AC: 563 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00469 AC: 319 AN: 68020

Other (OTH) AF: 0.0118 AC: 25 AN: 2116

Alfa AF: 0.00970 Hom.: 37

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
PhyloP100		1.7
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9644946; hg19: chr9-127685506; COSMIC: COSV107481964; COSMIC: COSV107481964;