16-70481102-A-T

Variant names:

• chr16-70481102-A-T
• rs113010015
• NM_015386.3:c.2278T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015386.3(COG4):​c.2278T>A​(p.Leu760Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: COG4 NM_015386.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21366292).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG4	NM_015386.3	c.2278T>A	p.Leu760Met	missense_variant	Exon 19 of 19	ENST00000323786.10	NP_056201.2
COG4	NM_001195139.2	c.2203T>A	p.Leu735Met	missense_variant	Exon 18 of 18		NP_001182068.2
COG4	NM_001365426.1	c.1852T>A	p.Leu618Met	missense_variant	Exon 20 of 20		NP_001352355.1
COG4	NR_158212.1	n.2237T>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.2278T>A	p.Leu760Met	missense_variant	Exon 19 of 19	1	NM_015386.3	ENSP00000315775.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74342

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0029	T;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.21	T;T;T
MetaSVM	Benign	-0.86	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.51	N;.;.
REVEL	Benign	0.22
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.45	T;T;T
Vest4		0.58
MVP		0.17
MPC		0.51
ClinPred		0.39	T
GERP RS		-6.3
gMVP		0.47

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: rs113010015; hg19: chr16-70515005;