NM_153603.4:c.406G>T

Variant names:

• chr16-23445077-C-A
• NM_153603.4:c.406G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_153603.4(COG7):​c.406G>T​(p.Ala136Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COG7 NM_153603.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.16

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG7	NM_153603.4	c.406G>T	p.Ala136Ser	missense_variant	Exon 3 of 17	ENST00000307149.10	NP_705831.1
COG7	XM_017023870.2	c.211G>T	p.Ala71Ser	missense_variant	Exon 3 of 17		XP_016879359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG7	ENST00000307149.10	c.406G>T	p.Ala136Ser	missense_variant	Exon 3 of 17	1	NM_153603.4	ENSP00000305442.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461624 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.21
Sift	Benign	0.51	T
Sift4G	Benign	0.17	T
Polyphen		0.97	D
Vest4		0.65
MutPred		0.51		Gain of helix (P = 0.0117);
MVP		0.41
MPC		0.31
ClinPred		0.86	D
GERP RS		4.6
Varity_R		0.066
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-23456398;