rs3812883

Variant names:

• chr13-39655820-T-A
• rs3812883
• NM_020751.3:c.94T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-39655820-T-A
• chr13-39655820-T-G

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.94T>A​(p.Cys32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,600,520 control chromosomes in the GnomAD database, including 140,288 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C32Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.44 (15022 hom., cov: 33)
  • Exomes 𝑓: 0.41 (125266 hom.)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 2.60
• Publications: 30 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, PanelApp Australia
• 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=1.9721554E-5).
• BP6: Variant 13-39655820-T-A is Benign according to our data. Variant chr13-39655820-T-A is described in ClinVar as Benign. ClinVar VariationId is 193437.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	NM_020751.3	MANE Select	c.94T>A	p.Cys32Ser	missense	Exon 1 of 19	NP_065802.1	Q9Y2V7-1
	COG6	NM_001145079.2		c.94T>A	p.Cys32Ser	missense	Exon 1 of 19	NP_001138551.1	A0A140VJG7
	COG6	NR_026745.1		n.194T>A		non_coding_transcript_exon	Exon 1 of 20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG6	ENST00000455146.8	TSL:1 MANE Select	c.94T>A	p.Cys32Ser	missense	Exon 1 of 19	ENSP00000397441.2	Q9Y2V7-1
	COG6	ENST00000416691.6	TSL:1	c.94T>A	p.Cys32Ser	missense	Exon 1 of 19	ENSP00000403733.1	Q9Y2V7-2
	COG6	ENST00000356576.8	TSL:1	n.94T>A		non_coding_transcript_exon	Exon 1 of 20	ENSP00000348983.4	Q9Y2V7-4

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66659 AN: 152014 Hom.: 15004 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.475

GnomAD2 exomes AF: 0.458 AC: 104169 AN: 227446 AF XY: 0.455

Gnomad AFR exome AF: 0.473

Gnomad AMR exome AF: 0.651

Gnomad ASJ exome AF: 0.471

Gnomad EAS exome AF: 0.436

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.449

GnomAD4 exome AF: 0.411 AC: 594656 AN: 1448386 Hom.: 125266 Cov.: 49 AF XY: 0.414 AC XY: 298060 AN XY: 719562

African (AFR) AF: 0.474 AC: 15692 AN: 33132

American (AMR) AF: 0.643 AC: 27753 AN: 43180

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12264 AN: 25930

East Asian (EAS) AF: 0.472 AC: 18392 AN: 39000

South Asian (SAS) AF: 0.547 AC: 46310 AN: 84622

European-Finnish (FIN) AF: 0.367 AC: 19055 AN: 51912

Middle Eastern (MID) AF: 0.547 AC: 2454 AN: 4486

European-Non Finnish (NFE) AF: 0.386 AC: 427129 AN: 1106380

Other (OTH) AF: 0.429 AC: 25607 AN: 59744

GnomAD4 genome AF: 0.439 AC: 66720 AN: 152134 Hom.: 15022 Cov.: 33 AF XY: 0.442 AC XY: 32888 AN XY: 74382

African (AFR) AF: 0.476 AC: 19746 AN: 41502

American (AMR) AF: 0.584 AC: 8938 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2330 AN: 5160

South Asian (SAS) AF: 0.523 AC: 2524 AN: 4822

European-Finnish (FIN) AF: 0.362 AC: 3841 AN: 10596

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

European-Non Finnish (NFE) AF: 0.385 AC: 26157 AN: 67962

Other (OTH) AF: 0.480 AC: 1015 AN: 2116

Alfa AF: 0.403 Hom.: 9724

Bravo AF: 0.456

TwinsUK AF: 0.388 AC: 1437

ALSPAC AF: 0.387 AC: 1493

ESP6500AA AF: 0.473 AC: 2079

ESP6500EA AF: 0.387 AC: 3324

ExAC AF: 0.434 AC: 52122

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	0.064
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.58
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.000020	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.2	N
PhyloP100		2.6
PrimateAI	Benign	0.35	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.073
Sift	Benign	0.92	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.038
MutPred		0.21		Gain of catalytic residue at T27 (P = 0.002)
MPC		0.062
ClinPred		0.0089	T
GERP RS		3.0
PromoterAI		0.0093	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.11
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: rs3812883; hg19: chr13-40229957; COSMIC: COSV62995068; COSMIC: COSV62995068;