NM_002077.4:c.2187G>C

Variant names:

• chr9-124881207-C-G
• rs1277647235
• NM_002077.4:c.2187G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002077.4(GOLGA1):​c.2187G>C​(p.Glu729Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000375 in 1,600,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: GOLGA1 NM_002077.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.356
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39709905).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002077.4. 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
	GOLGA1	NM_002077.4	MANE Select	c.2187G>C	p.Glu729Asp	missense	Exon 22 of 23	NP_002068.2	Q92805

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA1	ENST00000373555.9	TSL:1 MANE Select	c.2187G>C	p.Glu729Asp	missense	Exon 22 of 23	ENSP00000362656.4	Q92805
	GOLGA1	ENST00000876330.1		c.2220G>C	p.Glu740Asp	missense	Exon 23 of 24	ENSP00000546389.1
	GOLGA1	ENST00000876328.1		c.2187G>C	p.Glu729Asp	missense	Exon 22 of 23	ENSP00000546387.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1448778 Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2 AN XY: 721612

African (AFR) AF: 0.00 AC: 0 AN: 33272

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000455 AC: 5 AN: 1099960

Other (OTH) AF: 0.00 AC: 0 AN: 59952

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.092
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.36
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.56		Loss of disorder (P = 0.1176)
MVP		0.58
MPC		0.82
ClinPred		0.93	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.45
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1277647235; hg19: chr9-127643486;