chr13-39655763-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020751.3(COG6):​c.37G>A​(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,440,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

COG6
NM_020751.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.310
Variant links:
Genes affected
COG6 (HGNC:18621): (component of oligomeric golgi complex 6) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi apparatus. The encoded protein is organized with conserved oligomeric Golgi complex components 5, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0673787).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
COG6NM_020751.3 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/19 ENST00000455146.8
COG6NM_001145079.2 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/19
COG6XM_011535168.2 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/20
COG6NR_026745.1 linkuse as main transcriptn.137G>A non_coding_transcript_exon_variant 1/20

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
COG6ENST00000455146.8 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/191 NM_020751.3 P1Q9Y2V7-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000347
AC:
5
AN:
1440800
Hom.:
0
Cov.:
41
AF XY:
0.00000280
AC XY:
2
AN XY:
714908
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:
0.00
Gnomad4 OTH exome
AF:
0.0000841
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 30, 2023The c.37G>A (p.A13T) alteration is located in exon 1 (coding exon 1) of the COG6 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
COG6-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
3.5
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0089
.;T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.66
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.067
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.39
N;N;.
REVEL
Benign
0.031
Sift
Benign
0.14
T;T;.
Sift4G
Benign
0.37
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.13
MutPred
0.28
Gain of catalytic residue at A13 (P = 5e-04);Gain of catalytic residue at A13 (P = 5e-04);Gain of catalytic residue at A13 (P = 5e-04);
MVP
0.030
MPC
0.053
ClinPred
0.085
T
GERP RS
2.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.028
gMVP
0.36

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs886050224; hg19: chr13-40229900; COSMIC: COSV62998584; COSMIC: COSV62998584; API