14-70326444-G-C

Position:

• chr14-70326444-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016468.7(COX16):​c.210C>G​(p.Ile70Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: COX16 NM_016468.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.127

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04000643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX16	NM_016468.7	c.210C>G	p.Ile70Met	missense_variant	4/4	ENST00000389912.7	NP_057552.1
SYNJ2BP-COX16	NM_001202549.2	c.366C>G	p.Ile122Met	missense_variant	5/5		NP_001189478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX16	ENST00000389912.7	c.210C>G	p.Ile70Met	missense_variant	4/4	1	NM_016468.7	ENSP00000374562	P1
	ENST00000655620.1	n.713-16228G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

The c.210C>G (p.I70M) alteration is located in exon 4 (coding exon 4) of the COX16 gene. This alteration results from a C to G substitution at nucleotide position 210, causing the isoleucine (I) at amino acid position 70 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.14	T;.;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.74	T;T;.;T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.040	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.;.;.;.
MutationTaster	Benign	0.70	D
PROVEAN	Benign	-1.1	N;.;.;.;.
REVEL	Benign	0.020
Sift	Benign	0.24	T;.;.;.;.
Sift4G	Benign	0.35	T;T;.;.;.
Polyphen		0.016	B;.;.;.;.
Vest4		0.16
MutPred		0.15		Loss of methylation at K71 (P = 0.0332);.;.;.;.;
MVP		0.081
MPC		0.24
ClinPred		0.077	T
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.044
gMVP		0.30

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: chr14-70793161; COSMIC: COSV66303302;