Genetic Variant COG6:c.153+278T>C (chr13-39656157-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.82

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]

COG6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1220794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-39656157-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3 link	c.153+278T>C	intron_variant	Intron 1 of 18	ENST00000455146.8	NP_065802.1	Q9Y2V7-1A0A024RDW5
COG6	NM_001145079.2 link	c.153+278T>C	intron_variant	Intron 1 of 18		NP_001138551.1	Q9Y2V7-2A0A140VJG7
COG6	XM_011535168.2 link	c.153+278T>C	intron_variant	Intron 1 of 19		XP_011533470.1
COG6	NR_026745.1 link	n.253+278T>C	intron_variant	Intron 1 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8 link	c.153+278T>C		intron_variant	Intron 1 of 18	1	NM_020751.3	ENSP00000397441.2		Q9Y2V7-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67102

AN:

151872

Hom.:

15246

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.481

AC:

61896

AN:

128802

Hom.:

15659

AF XY:

0.478

AC XY:

33723

AN XY:

70514

show subpopulations

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 SAS exome

AF:

0.549

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.:

AF XY:

0.443

AC XY:

108393

AN XY:

244876

show subpopulations

Gnomad4 AFR exome

AF:

0.479

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.471

Gnomad4 EAS exome

AF:

0.467

Gnomad4 SAS exome

AF:

0.549

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.383

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.442

AC:

67164

AN:

151990

Hom.:

15265

Cov.:

AF XY:

0.445

AC XY:

33051

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.585

Gnomad4 ASJ

AF:

0.459

Gnomad4 EAS

AF:

0.450

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.389

Hom.:

6012

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

LINK: link

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

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over