13-39656157-T-C

Variant names:

• chr13-39656157-T-C
• rs3812888
• NM_020751.3:c.153+278T>C

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.153+278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 598,416 control chromosomes in the GnomAD database, including 59,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15265 hom., cov: 32)
  • Exomes 𝑓: 0.44 (44571 hom.)
• Consequence: COG6 NM_020751.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.82
• Publications: 6 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 (BayesDel_noAF=-0.9).
• BP6: Variant 13-39656157-T-C is Benign according to our data. Variant chr13-39656157-T-C is described in ClinVar as Benign. ClinVar VariationId is 1220794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.153+278T>C		intron_variant	Intron 1 of 18	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.153+278T>C		intron_variant	Intron 1 of 18		NP_001138551.1
COG6	NR_026745.1	n.253+278T>C		intron_variant	Intron 1 of 19
COG6	XM_011535168.2	c.153+278T>C		intron_variant	Intron 1 of 19		XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.153+278T>C		intron_variant	Intron 1 of 18	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67102 AN: 151872 Hom.: 15246 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.478

GnomAD2 exomes AF: 0.481 AC: 61896 AN: 128802 AF XY: 0.478

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.644

Gnomad ASJ exome AF: 0.474

Gnomad EAS exome AF: 0.437

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.437 AC: 195301 AN: 446426 Hom.: 44571 Cov.: 2 AF XY: 0.443 AC XY: 108393 AN XY: 244876

African (AFR) AF: 0.479 AC: 6399 AN: 13364

American (AMR) AF: 0.639 AC: 19995 AN: 31270

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 7911 AN: 16794

East Asian (EAS) AF: 0.467 AC: 10485 AN: 22440

South Asian (SAS) AF: 0.549 AC: 33517 AN: 61004

European-Finnish (FIN) AF: 0.361 AC: 8156 AN: 22584

Middle Eastern (MID) AF: 0.536 AC: 1905 AN: 3554

European-Non Finnish (NFE) AF: 0.383 AC: 96300 AN: 251314

Other (OTH) AF: 0.441 AC: 10633 AN: 24102

GnomAD4 genome AF: 0.442 AC: 67164 AN: 151990 Hom.: 15265 Cov.: 32 AF XY: 0.445 AC XY: 33051 AN XY: 74290

African (AFR) AF: 0.488 AC: 20229 AN: 41462

American (AMR) AF: 0.585 AC: 8934 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2320 AN: 5150

South Asian (SAS) AF: 0.523 AC: 2514 AN: 4810

European-Finnish (FIN) AF: 0.361 AC: 3814 AN: 10558

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

European-Non Finnish (NFE) AF: 0.385 AC: 26171 AN: 67966

Other (OTH) AF: 0.483 AC: 1014 AN: 2100

Alfa AF: 0.390 Hom.: 6670

Bravo AF: 0.460

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.62
PhyloP100		-1.8
PromoterAI		-0.030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3812888; hg19: chr13-40230294;