NM_006348.5:c.*1637G>A

Variant names:

• chr7-107201879-C-T
• rs147954001
• NM_006348.5:c.*1637G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_006348.5(COG5):​c.*1637G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 153,454 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: COG5 NM_006348.5 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.554
• Publications: 0 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 7-107201879-C-T is Benign according to our data. Variant chr7-107201879-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 358435.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00439 (668/152312) while in subpopulation AMR AF = 0.0101 (155/15290). AF 95% confidence interval is 0.00884. There are 4 homozygotes in GnomAd4. There are 331 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.*1637G>A		3_prime_UTR	Exon 22 of 22	NP_006339.4
	HBP1	NM_012257.4	MANE Select	c.*448C>T		3_prime_UTR	Exon 11 of 11	NP_036389.2
	COG5	NM_181733.4		c.*1637G>A		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.*1637G>A		3_prime_UTR	Exon 22 of 22	ENSP00000297135.4	Q9UP83-4
	HBP1	ENST00000222574.9	TSL:1 MANE Select	c.*448C>T		3_prime_UTR	Exon 11 of 11	ENSP00000222574.4	O60381-1
	COG5	ENST00000347053.8	TSL:1	c.*1637G>A		3_prime_UTR	Exon 21 of 21	ENSP00000334703.3	A0AAA9X096

Frequencies

GnomAD3 genomes AF: 0.00439 AC: 668 AN: 152194 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00350 AC: 4 AN: 1142 Hom.: 0 Cov.: 0 AF XY: 0.00450 AC XY: 3 AN XY: 666

African (AFR) AF: 0.00 AC: 0 AN: 24

American (AMR) AF: 0.00 AC: 0 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 1 AN: 14

East Asian (EAS) AF: 0.00 AC: 0 AN: 26

South Asian (SAS) AF: 0.00 AC: 0 AN: 22

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 438

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00534 AC: 3 AN: 562

Other (OTH) AF: 0.00 AC: 0 AN: 26

GnomAD4 genome AF: 0.00439 AC: 668 AN: 152312 Hom.: 4 Cov.: 33 AF XY: 0.00444 AC XY: 331 AN XY: 74486

African (AFR) AF: 0.00459 AC: 191 AN: 41568

American (AMR) AF: 0.0101 AC: 155 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0208 AC: 72 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00323 AC: 220 AN: 68038

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00360 Hom.: 0

Bravo AF: 0.00581

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	-	COG5-congenital disorder of glycosylation (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.9
DANN	Benign	0.80
PhyloP100		0.55
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: rs147954001; hg19: chr7-106842324;