9-124889170-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002077.4(GOLGA1):c.1734C>T(p.Ala578=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00582 in 1,611,718 control chromosomes in the GnomAD database, including 375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (225 hom., cov: 33)
  • Exomes 𝑓: 0.0034 (150 hom.)
• Consequence: GOLGA1 NM_002077.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 9-124889170-G-A is Benign according to our data. Variant chr9-124889170-G-A is described in ClinVar as [Benign]. Clinvar id is 776450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GOLGA1	NM_002077.4	c.1734C>T	p.Ala578=	synonymous_variant	18/23	ENST00000373555.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GOLGA1	ENST00000373555.9	c.1734C>T	p.Ala578=	synonymous_variant	18/23	1	NM_002077.4	P1
GOLGA1	ENST00000475407.5	c.*880C>T		3_prime_UTR_variant, NMD_transcript_variant	13/18	5
GOLGA1	ENST00000485337.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0289 AC: 4401 AN: 152160 Hom.: 224 Cov.: 33

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.00836 AC: 2088 AN: 249826 Hom.: 81 AF XY: 0.00654 AC XY: 883 AN XY: 135040

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00696

Gnomad ASJ exome AF: 0.00510

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000968

Gnomad OTH exome AF: 0.00476

GnomAD4 exome AF: 0.00340 AC: 4968 AN: 1459440 Hom.: 150 Cov.: 32 AF XY: 0.00310 AC XY: 2253 AN XY: 725976

Gnomad4 AFR exome AF: 0.0956

Gnomad4 AMR exome AF: 0.00766

Gnomad4 ASJ exome AF: 0.00444

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000694

Gnomad4 OTH exome AF: 0.00766

GnomAD4 genome AF: 0.0290 AC: 4420 AN: 152278 Hom.: 225 Cov.: 33 AF XY: 0.0284 AC XY: 2117 AN XY: 74458

Gnomad4 AFR AF: 0.0971

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0112 Hom.: 46

Bravo AF: 0.0337

EpiCase AF: 0.00131

EpiControl AF: 0.00148

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.54
Dann	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs34090990; hg19: chr9-127651449;