chr13-39655754-G-T

Variant names:

• chr13-39655754-G-T
• rs3812882
• NM_020751.3:c.28G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020751.3(COG6):​c.28G>T​(p.Ala10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,592,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: COG6 NM_020751.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04500729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG6	NM_020751.3	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 19	ENST00000455146.8	NP_065802.1
COG6	NM_001145079.2	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 19		NP_001138551.1
COG6	XM_011535168.2	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 20		XP_011533470.1
COG6	NR_026745.1	n.128G>T		non_coding_transcript_exon_variant	Exon 1 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG6	ENST00000455146.8	c.28G>T	p.Ala10Ser	missense_variant	Exon 1 of 19	1	NM_020751.3	ENSP00000397441.2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152110 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: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000237 AC: 5 AN: 210934 Hom.: 0 AF XY: 0.0000261 AC XY: 3 AN XY: 114932

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000314

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: 0.0000174 AC: 25 AN: 1439892 Hom.: 0 Cov.: 43 AF XY: 0.0000182 AC XY: 13 AN XY: 714356

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000625

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000168

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152228 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74426

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ExAC AF: 0.0000169 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0083	.;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.080	N;N;.
REVEL	Benign	0.014
Sift	Benign	0.054	T;T;.
Sift4G	Benign	0.62	T;T;D
Polyphen		0.0010	.;B;.
Vest4		0.19
MutPred		0.25		Gain of catalytic residue at T14 (P = 0.0229);Gain of catalytic residue at T14 (P = 0.0229);Gain of catalytic residue at T14 (P = 0.0229);
MVP		0.076
MPC		0.050
ClinPred		0.081	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.088
gMVP		0.25

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

Publications

LitVar

Other links and lift over

dbSNP: rs3812882; hg19: chr13-40229891;