chr9-124881885-G-T

Variant names:

• chr9-124881885-G-T
• rs145763272
• NM_002077.4:c.2035C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002077.4(GOLGA1):​c.2035C>A​(p.Pro679Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P679S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GOLGA1 NM_002077.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07005036).

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.2035C>A	p.Pro679Thr	missense	Exon 21 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.2035C>A	p.Pro679Thr	missense	Exon 21 of 23	ENSP00000362656.4	Q92805
	GOLGA1	ENST00000876330.1		c.2068C>A	p.Pro690Thr	missense	Exon 22 of 24	ENSP00000546389.1
	GOLGA1	ENST00000876328.1		c.2035C>A	p.Pro679Thr	missense	Exon 21 of 23	ENSP00000546387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459992 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726400

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110510

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	15
DANN	Benign	0.81
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.81
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.017
Sift	Benign	0.46	T
Sift4G	Benign	0.36	T
Polyphen		0.051	B
Vest4		0.098
MutPred		0.29		Gain of glycosylation at P679 (P = 0.0254)
MVP		0.45
MPC		0.27
ClinPred		0.053	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.26
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs145763272; hg19: chr9-127644164;