7-107563544-TGGG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006348.5(COG5):c.94+256_94+258del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 254,514 control chromosomes in the GnomAD database, including 66 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (53 hom., cov: 0)
  • Exomes 𝑓: 0.029 (13 hom.)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150

Genes affected

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

DUS4L (HGNC:21517): (dihydrouridine synthase 4 like) Predicted to enable tRNA dihydrouridine synthase activity. Predicted to be involved in tRNA dihydrouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-107563544-TGGG-T is Benign according to our data. Variant chr7-107563544-TGGG-T is described in ClinVar as [Benign]. Clinvar id is 1281581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COG5	NM_006348.5	c.94+256_94+258del		intron_variant		ENST00000297135.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG5	ENST00000297135.9	c.94+256_94+258del		intron_variant		1	NM_006348.5	P2

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 1364 AN: 59168 Hom.: 54 Cov.: 0

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00874

Gnomad ASJ AF: 0.000760

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00319

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0160

GnomAD4 exome AF: 0.0292 AC: 5703 AN: 195284 Hom.: 13 AF XY: 0.0276 AC XY: 2879 AN XY: 104184

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.0368

Gnomad4 ASJ exome AF: 0.0217

Gnomad4 EAS exome AF: 0.0483

Gnomad4 SAS exome AF: 0.0197

Gnomad4 FIN exome AF: 0.0255

Gnomad4 NFE exome AF: 0.0242

Gnomad4 OTH exome AF: 0.0279

GnomAD4 genome AF: 0.0230 AC: 1364 AN: 59230 Hom.: 53 Cov.: 0 AF XY: 0.0231 AC XY: 642 AN XY: 27736

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.00873

Gnomad4 ASJ AF: 0.000760

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00319

Gnomad4 NFE AF: 0.00118

Gnomad4 OTH AF: 0.0160

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs71134268; hg19: chr7-107203989;