chr17-73208293-TTTCTC-T

Position:

• chr17-73208293-TTTCTC-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018714.3(COG1):​c.2806-19_2806-15del variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00000479 in 1,460,342 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: COG1 NM_018714.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00

Genes affected

FAM104A (HGNC:25918): (VCP nuclear cofactor family member 1)

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) 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. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM104A	NM_001098832.2	c.*1231_*1235del		3_prime_UTR_variant	4/4	ENST00000405159.8
COG1	NM_018714.3	c.2806-19_2806-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000299886.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM104A	ENST00000405159.8	c.*1231_*1235del		3_prime_UTR_variant	4/4	1	NM_001098832.2
COG1	ENST00000299886.9	c.2806-19_2806-15del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_018714.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251338 Hom.: 0 AF XY: 0.0000147 AC XY: 2 AN XY: 135852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460342 Hom.: 0 AF XY: 0.00000413 AC XY: 3 AN XY: 726504

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

COG1 congenital disorder of glycosylation Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 11, 2022

This sequence change falls in intron 13 of the COG1 gene. It does not directly change the encoded amino acid sequence of the COG1 protein. This variant is present in population databases (rs764085125, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with COG1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs764085125; hg19: chr17-71204432;