Variant 14-70326449-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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

Variant links:

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]

COX16 links:

SYNJ2BP-COX16 (HGNC:):

SYNJ2BP-COX16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.208278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX16	NM_016468.7 linkuse as main transcript	c.205A>G	p.Lys69Glu	missense_variant, splice_region_variant	4/4	ENST00000389912.7	NP_057552.1
SYNJ2BP-COX16	NM_001202549.2 linkuse as main transcript	c.361A>G	p.Lys121Glu	missense_variant, splice_region_variant	5/5		NP_001189478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX16	ENST00000389912.7 linkuse as main transcript	c.205A>G	p.Lys69Glu	missense_variant, splice_region_variant	4/4	1	NM_016468.7	ENSP00000374562	P1
	ENST00000655620.1 linkuse as main transcript	n.713-16223T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000605

AC:

AN:

214824

Hom.:

AF XY:

0.0000513

AC XY:

AN XY:

117058

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

705828

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000128

Gnomad4 FIN exome

AF:

0.0000384

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.0000687

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.205A>G (p.K69E) alteration is located in exon 4 (coding exon 4) of the COX16 gene. This alteration results from a A to G substitution at nucleotide position 205, causing the lysine (K) at amino acid position 69 to be replaced by a glutamic acid (E). 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

0.24

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;.;.;.;.

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.72

T;T;.;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.21

T;T;T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.9

L;.;.;.;.

MutationTaster

Benign

1.0

PROVEAN

Uncertain

-3.2

D;.;.;.;.

REVEL

Benign

0.21

Sift

Benign

0.067

T;.;.;.;.

Sift4G

Benign

0.085

T;T;.;.;.

Polyphen

0.88

P;.;.;.;.

Vest4

0.49

MVP

0.22

MPC

0.42

ClinPred

0.25

GERP RS

5.6

Varity_R

0.34

gMVP

0.45

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over