chr9-124881920-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002077.4(GOLGA1):​c.2000G>T​(p.Arg667Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R667Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GOLGA1
NM_002077.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35275728).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GOLGA1NM_002077.4 linkc.2000G>T p.Arg667Leu missense_variant Exon 21 of 23 ENST00000373555.9 NP_002068.2 Q92805A0A024R869

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GOLGA1ENST00000373555.9 linkc.2000G>T p.Arg667Leu missense_variant Exon 21 of 23 1 NM_002077.4 ENSP00000362656.4 Q92805
GOLGA1ENST00000475407.5 linkn.*1146G>T non_coding_transcript_exon_variant Exon 16 of 18 5 ENSP00000473648.1 R4GNH1
GOLGA1ENST00000475407.5 linkn.*1146G>T 3_prime_UTR_variant Exon 16 of 18 5 ENSP00000473648.1 R4GNH1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458662
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725824
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.35
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.14
Sift
Benign
0.11
T
Sift4G
Benign
0.14
T
Polyphen
1.0
D
Vest4
0.42
MutPred
0.28
Gain of glycosylation at K669 (P = 0.0946);
MVP
0.67
MPC
0.96
ClinPred
0.97
D
GERP RS
5.8
Varity_R
0.13
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-127644199; API