9-124889277-G-T

Variant names:

• chr9-124889277-G-T
• rs1320651150
• NM_002077.4:c.1627C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002077.4(GOLGA1):​c.1627C>A​(p.His543Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GOLGA1 NM_002077.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16646522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOLGA1	NM_002077.4	c.1627C>A	p.His543Asn	missense_variant	Exon 18 of 23	ENST00000373555.9	NP_002068.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOLGA1	ENST00000373555.9	c.1627C>A	p.His543Asn	missense_variant	Exon 18 of 23	1	NM_002077.4	ENSP00000362656.4
GOLGA1	ENST00000485337.1	n.*381C>A		non_coding_transcript_exon_variant	Exon 10 of 10	5		ENSP00000435006.1
GOLGA1	ENST00000485337.1	n.*381C>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000435006.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461536 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727100

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1627C>A (p.H543N) alteration is located in exon 18 (coding exon 16) of the GOLGA1 gene. This alteration results from a C to A substitution at nucleotide position 1627, causing the histidine (H) at amino acid position 543 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.055
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.10
Sift	Benign	0.44	T
Sift4G	Benign	0.37	T
Polyphen		0.55	P
Vest4		0.32
MutPred		0.16		Loss of catalytic residue at L545 (P = 0.0683);
MVP		0.39
MPC		0.67
ClinPred		0.60	D
GERP RS		5.5
Varity_R		0.091
gMVP		0.16

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: rs1320651150; hg19: chr9-127651556;