rs374821573

Variant names:

• chr13-39655684-C-A
• rs374821573
• NM_020751.3:c.-43C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-39655684-C-A
• chr13-39655684-C-G
• chr13-39655684-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020751.3(COG6):​c.-43C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,554,936 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: 𝑓 0.0000069 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: COG6 NM_020751.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.-43C>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1
COG6	NM_020751.3	c.-43C>A		5_prime_UTR_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.-43C>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2
COG6	ENST00000455146.8	c.-43C>A		5_prime_UTR_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.00000687 AC: 1 AN: 145550 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000233

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000426 AC: 6 AN: 1409386 Hom.: 0 Cov.: 30 AF XY: 0.00000718 AC XY: 5 AN XY: 696444

African (AFR) AF: 0.00 AC: 0 AN: 31990

American (AMR) AF: 0.0000260 AC: 1 AN: 38466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25354

East Asian (EAS) AF: 0.00 AC: 0 AN: 36454

South Asian (SAS) AF: 0.0000372 AC: 3 AN: 80618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083782

Other (OTH) AF: 0.0000343 AC: 2 AN: 58278

GnomAD4 genome AF: 0.00000687 AC: 1 AN: 145550 Hom.: 0 Cov.: 34 AF XY: 0.0000141 AC XY: 1 AN XY: 70778

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39724

American (AMR) AF: 0.00 AC: 0 AN: 13714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3394

East Asian (EAS) AF: 0.00 AC: 0 AN: 4838

South Asian (SAS) AF: 0.000233 AC: 1 AN: 4290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66306

Other (OTH) AF: 0.00 AC: 0 AN: 1960

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		0.084
PromoterAI		-0.084	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs374821573; hg19: chr13-40229821;