9-86035593-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016548.4(GOLM1):​c.790G>A​(p.Glu264Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,078 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E264A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GOLM1
NM_016548.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.96
Variant links:
Genes affected
GOLM1 (HGNC:15451): (golgi membrane protein 1) The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The protein encoded by this gene is a type II Golgi transmembrane protein. It processes proteins synthesized in the rough endoplasmic reticulum and assists in the transport of protein cargo through the Golgi apparatus. The expression of this gene has been observed to be upregulated in response to viral infection. Alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

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=0.15357912).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GOLM1NM_016548.4 linkc.790G>A p.Glu264Lys missense_variant Exon 8 of 10 ENST00000388712.7 NP_057632.2 Q8NBJ4-1B3KNK9
GOLM1NM_177937.3 linkc.790G>A p.Glu264Lys missense_variant Exon 8 of 10 NP_808800.1 Q8NBJ4-1B3KNK9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GOLM1ENST00000388712.7 linkc.790G>A p.Glu264Lys missense_variant Exon 8 of 10 1 NM_016548.4 ENSP00000373364.3 Q8NBJ4-1
GOLM1ENST00000388711.7 linkc.790G>A p.Glu264Lys missense_variant Exon 8 of 10 1 ENSP00000373363.3 Q8NBJ4-1
GOLM1ENST00000257504.10 linkn.789G>A non_coding_transcript_exon_variant Exon 7 of 7 5
GOLM1ENST00000464314.1 linkn.499G>A non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1453078
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
723284
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
29

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.790G>A (p.E264K) alteration is located in exon 8 (coding exon 7) of the GOLM1 gene. This alteration results from a G to A substitution at nucleotide position 790, causing the glutamic acid (E) at amino acid position 264 to be replaced by a lysine (K). 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
0.078
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.045
T;T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.18
N
LIST_S2
Benign
0.35
.;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.86
N;N
REVEL
Benign
0.080
Sift
Benign
0.45
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.72
P;P
Vest4
0.41
MutPred
0.26
Gain of ubiquitination at E264 (P = 0.0014);Gain of ubiquitination at E264 (P = 0.0014);
MVP
0.53
MPC
0.15
ClinPred
0.40
T
GERP RS
3.7
Varity_R
0.075
gMVP
0.18

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: chr9-88650508; API