rs773755170

Variant names:

• chr7-107201796-T-C
• rs773755170
• NM_006348.5:c.*1720A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-107201796-T-C
• chr7-107201796-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006348.5(COG5):​c.*1720A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 184,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: COG5 NM_006348.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.224
• Publications: 1 publications found

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]

HBP1 (HGNC:23200): (HMG-box transcription factor 1) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of lipid transport; negative regulation of reactive oxygen species biosynthetic process; and negative regulation of transcription by RNA polymerase II. Located in nuclear speck. Biomarker of osteoarthritis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006348.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	NM_006348.5	MANE Select	c.*1720A>G		3_prime_UTR	Exon 22 of 22	NP_006339.4
	HBP1	NM_012257.4	MANE Select	c.*365T>C		3_prime_UTR	Exon 11 of 11	NP_036389.2
	COG5	NM_181733.4		c.*1720A>G		3_prime_UTR	Exon 21 of 21	NP_859422.3	A0AAA9X096

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.*1720A>G		3_prime_UTR	Exon 22 of 22	ENSP00000297135.4	Q9UP83-4
	HBP1	ENST00000222574.9	TSL:1 MANE Select	c.*365T>C		3_prime_UTR	Exon 11 of 11	ENSP00000222574.4	O60381-1
	COG5	ENST00000347053.8	TSL:1	c.*1720A>G		3_prime_UTR	Exon 21 of 21	ENSP00000334703.3	A0AAA9X096

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152240 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000432 AC: 14 AN: 32418 Hom.: 0 Cov.: 0 AF XY: 0.000539 AC XY: 9 AN XY: 16690

African (AFR) AF: 0.00 AC: 0 AN: 1162

American (AMR) AF: 0.00 AC: 0 AN: 1394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1284

East Asian (EAS) AF: 0.00 AC: 0 AN: 2076

South Asian (SAS) AF: 0.00 AC: 0 AN: 1554

European-Finnish (FIN) AF: 0.000607 AC: 1 AN: 1648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 168

European-Non Finnish (NFE) AF: 0.000573 AC: 12 AN: 20946

Other (OTH) AF: 0.000457 AC: 1 AN: 2186

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15 AN XY: 74382

African (AFR) AF: 0.000145 AC: 6 AN: 41460

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000530 Hom.: 0

Bravo AF: 0.000249

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	COG5-congenital disorder of glycosylation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism

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: rs773755170; hg19: chr7-106842241; COSMIC: COSV108072960; COSMIC: COSV108072960;