rs3812882

Variant names:

• chr13-39655754-G-A
• rs3812882
• NM_020751.3:c.28G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-39655754-G-A
• chr13-39655754-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_020751.3(COG6):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 1,591,734 control chromosomes in the GnomAD database, including 140,263 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15026 hom., cov: 34)
  • Exomes 𝑓: 0.41 (125237 hom.)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.101
• Publications: 29 publications found

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]

COG6 Gene-Disease associations (from GenCC):

• COG6-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4144059E-5).
• BP6: Variant 13-39655754-G-A is Benign according to our data. Variant chr13-39655754-G-A is described in ClinVar as Benign. ClinVar VariationId is 193436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020751.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	NM_020751.3	MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 19	NP_065802.1
	COG6	NM_001145079.2		c.28G>A	p.Ala10Thr	missense	Exon 1 of 19	NP_001138551.1
	COG6	NR_026745.1		n.128G>A		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.28G>A	p.Ala10Thr	missense	Exon 1 of 19	ENSP00000397441.2
	COG6	ENST00000416691.6	TSL:1	c.28G>A	p.Ala10Thr	missense	Exon 1 of 19	ENSP00000403733.1
	COG6	ENST00000356576.8	TSL:1	n.28G>A		non_coding_transcript_exon	Exon 1 of 20	ENSP00000348983.4

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66684 AN: 152068 Hom.: 15008 Cov.: 34

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.475

GnomAD2 exomes AF: 0.475 AC: 100290 AN: 210934 AF XY: 0.471

Gnomad AFR exome AF: 0.500

Gnomad AMR exome AF: 0.661

Gnomad ASJ exome AF: 0.475

Gnomad EAS exome AF: 0.449

Gnomad FIN exome AF: 0.375

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.412 AC: 592562 AN: 1439548 Hom.: 125237 Cov.: 43 AF XY: 0.415 AC XY: 296728 AN XY: 714206

African (AFR) AF: 0.474 AC: 15633 AN: 32956

American (AMR) AF: 0.649 AC: 27689 AN: 42668

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 12203 AN: 25768

East Asian (EAS) AF: 0.474 AC: 18210 AN: 38396

South Asian (SAS) AF: 0.548 AC: 45887 AN: 83678

European-Finnish (FIN) AF: 0.370 AC: 18704 AN: 50586

Middle Eastern (MID) AF: 0.537 AC: 2714 AN: 5050

European-Non Finnish (NFE) AF: 0.387 AC: 425989 AN: 1101044

Other (OTH) AF: 0.430 AC: 25533 AN: 59402

GnomAD4 genome AF: 0.439 AC: 66745 AN: 152186 Hom.: 15026 Cov.: 34 AF XY: 0.442 AC XY: 32894 AN XY: 74400

African (AFR) AF: 0.476 AC: 19769 AN: 41528

American (AMR) AF: 0.584 AC: 8941 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1595 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2323 AN: 5160

South Asian (SAS) AF: 0.523 AC: 2520 AN: 4820

European-Finnish (FIN) AF: 0.362 AC: 3839 AN: 10604

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26170 AN: 67982

Other (OTH) AF: 0.480 AC: 1014 AN: 2114

Alfa AF: 0.405 Hom.: 28961

Bravo AF: 0.456

TwinsUK AF: 0.388 AC: 1438

ALSPAC AF: 0.388 AC: 1494

ESP6500AA AF: 0.494 AC: 2156

ESP6500EA AF: 0.409 AC: 3484

ExAC AF: 0.441 AC: 52046

Asia WGS AF: 0.514 AC: 1786 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	COG6-congenital disorder of glycosylation (2)
-	-	1	COG6-congenital disorder of glycosylation;C3809160:Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (1)
-	-	1	Hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.000014	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.10
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.029
Sift	Benign	0.18	T
Sift4G	Benign	0.36	T
Polyphen		0.0030	B
Vest4		0.099
MPC		0.054
ClinPred		0.034	T
GERP RS		2.7
PromoterAI		-0.046	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.067
gMVP		0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs3812882; hg19: chr13-40229891; COSMIC: COSV62995992; COSMIC: COSV62995992;