rs534007509

Variant names:

• chr13-39655674-T-C
• rs534007509
• NM_020751.3:c.-53T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-39655674-T-C
• chr13-39655674-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020751.3(COG6):​c.-53T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: COG6 NM_020751.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.-53T>C		5_prime_UTR_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1
COG6	NR_026745.1	n.48T>C		non_coding_transcript_exon_variant	Exon 1 of 20
COG6	NM_001145079.2	c.-53T>C		5_prime_UTR_variant	Exon 1 of 19		NP_001138551.1
COG6	XM_011535168.2	c.-53T>C		5_prime_UTR_variant	Exon 1 of 20		XP_011533470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.-53T>C		5_prime_UTR_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000642 AC: 1 AN: 155796 AF XY: 0.0000119

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000118

Gnomad EAS 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: 0.00000143 AC: 2 AN: 1399038 Hom.: 0 Cov.: 30 AF XY: 0.00000289 AC XY: 2 AN XY: 690960

African (AFR) AF: 0.00 AC: 0 AN: 31638

American (AMR) AF: 0.00 AC: 0 AN: 36934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 36018

South Asian (SAS) AF: 0.00 AC: 0 AN: 79762

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077674

Other (OTH) AF: 0.0000172 AC: 1 AN: 57976

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000225 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
DANN	Benign	0.44
PhyloP100		0.54
PromoterAI		-0.032	Neutral

Splicing

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

Other links and lift over

dbSNP: rs534007509; hg19: chr13-40229811;