14-70326449-T-C

Variant names:

• chr14-70326449-T-C
• rs756319016
• NM_016468.7:c.205A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016468.7(COX16):​c.205A>G​(p.Lys69Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000109 in 1,572,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: COX16 NM_016468.7 missense, splice_region
• Scores: Splicing: ADA: 0.7362
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 0 publications found

Genes affected

COX16 (HGNC:20213): (cytochrome c oxidase assembly factor COX16) Involved in mitochondrial cytochrome c oxidase assembly. Is integral component of mitochondrial inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

SYNJ2BP-COX16 (HGNC:48350): (SYNJ2BP-COX16 readthrough) This locus represents naturally occurring read-through transcription between the neighboring SYNJ2BP (synaptojanin 2 binding protein) and COX16 (COX16 cytochrome c oxidase assembly homolog (S. cerevisiae)) genes on chromosome 14. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2011]

ENSG00000259033 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.208278).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016468.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX16	NM_016468.7	MANE Select	c.205A>G	p.Lys69Glu	missense splice_region	Exon 4 of 4	NP_057552.1	Q9P0S2
	SYNJ2BP-COX16	NM_001202547.2		c.460A>G	p.Lys154Glu	missense splice_region	Exon 6 of 6	NP_001189476.1
	SYNJ2BP-COX16	NM_001202548.2		c.433A>G	p.Lys145Glu	missense splice_region	Exon 6 of 6	NP_001189477.1	A0A087WYV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COX16	ENST00000389912.7	TSL:1 MANE Select	c.205A>G	p.Lys69Glu	missense splice_region	Exon 4 of 4	ENSP00000374562.5	Q9P0S2
	SYNJ2BP-COX16	ENST00000621525.4	TSL:2	c.433A>G	p.Lys145Glu	missense splice_region	Exon 6 of 6	ENSP00000482133.1	A0A087WYV9
	SYNJ2BP-COX16	ENST00000617124.4	TSL:2	c.361A>G	p.Lys121Glu	missense splice_region	Exon 5 of 5	ENSP00000484161.1	A0A087X1F5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000605 AC: 13 AN: 214824 AF XY: 0.0000513

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000483

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000118 AC: 168 AN: 1419890 Hom.: 0 Cov.: 31 AF XY: 0.000112 AC XY: 79 AN XY: 705828

African (AFR) AF: 0.00 AC: 0 AN: 30926

American (AMR) AF: 0.00 AC: 0 AN: 35568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24350

East Asian (EAS) AF: 0.00 AC: 0 AN: 38712

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78154

European-Finnish (FIN) AF: 0.0000384 AC: 2 AN: 52144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5550

European-Non Finnish (NFE) AF: 0.000147 AC: 161 AN: 1096222

Other (OTH) AF: 0.0000687 AC: 4 AN: 58264

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.0000241 AC: 1 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000340

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.21
Sift	Benign	0.067	T
Sift4G	Benign	0.085	T
Polyphen		0.88	P
Vest4		0.49
MVP		0.22
MPC		0.42
ClinPred		0.25	T
GERP RS		5.6
Varity_R		0.34
gMVP		0.45
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.74
dbscSNV1_RF	Benign	0.45
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: rs756319016; hg19: chr14-70793166;