chr16-70514394-G-C

Variant names:

• chr16-70514394-G-C
• rs3931036
• NM_015386.3:c.485C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015386.3(COG4):​c.485C>G​(p.Thr162Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 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. T162I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: COG4 NM_015386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.02
• Publications: 47 publications found

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

COG4 Gene-Disease associations (from GenCC):

• COG4-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, PanelApp Australia, Ambry Genetics
• microcephalic osteodysplastic dysplasia, Saul-Wilson type

  Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18226591).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG4	NM_015386.3	c.485C>G	p.Thr162Ser	missense_variant	Exon 4 of 19	ENST00000323786.10	NP_056201.2
COG4	NM_001195139.2	c.473C>G	p.Thr158Ser	missense_variant	Exon 4 of 18		NP_001182068.2
COG4	NM_001365426.1	c.59C>G	p.Thr20Ser	missense_variant	Exon 5 of 20		NP_001352355.1
COG4	NR_158212.1	n.496C>G		non_coding_transcript_exon_variant	Exon 4 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10	c.485C>G	p.Thr162Ser	missense_variant	Exon 4 of 19	1	NM_015386.3	ENSP00000315775.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.091
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	D;D;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		7.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.3	N;.;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D;.;D;.
Sift4G	Uncertain	0.0020	D;D;D;.
Vest4		0.23
MVP		0.088
MPC		0.13
ClinPred		0.66	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.48

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: rs3931036; hg19: chr16-70548297;