chr16-70481062-A-T

Variant names:

• chr16-70481062-A-T
• NM_015386.3:c.2318T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015386.3(COG4):​c.2318T>A​(p.Leu773Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COG4 NM_015386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.857

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG4	NM_015386.3	c.2318T>A	p.Leu773Gln	missense_variant	Exon 19 of 19	ENST00000323786.10	NP_056201.2
COG4	NM_001195139.2	c.2243T>A	p.Leu748Gln	missense_variant	Exon 18 of 18		NP_001182068.2
COG4	NM_001365426.1	c.1892T>A	p.Leu631Gln	missense_variant	Exon 20 of 20		NP_001352355.1
COG4	NR_158212.1	n.2277T>A		non_coding_transcript_exon_variant	Exon 19 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10	c.2318T>A	p.Leu773Gln	missense_variant	Exon 19 of 19	1	NM_015386.3	ENSP00000315775.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461034 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726830

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T;T
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.13	D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.0	D;.;.
REVEL	Pathogenic	0.76
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0020	D;D;D
Vest4		0.93
MVP		0.92
MPC		0.66
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
gMVP		0.90

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: chr16-70514965;