Variant 14-70329184-G-A 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.194C>T(p.Ser65Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000664 in 1,596,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

COX16
NM_016468.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10

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=0.123927236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COX16	NM_016468.7 linkuse as main transcript	c.194C>T	p.Ser65Leu	missense_variant	3/4	ENST00000389912.7	NP_057552.1
SYNJ2BP-COX16	NM_001202549.2 linkuse as main transcript	c.350C>T	p.Ser117Leu	missense_variant	4/5		NP_001189478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COX16	ENST00000389912.7 linkuse as main transcript	c.194C>T	p.Ser65Leu	missense_variant	3/4	1	NM_016468.7	ENSP00000374562	P1
	ENST00000655620.1 linkuse as main transcript	n.713-13488G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000245

AC:

AN:

151204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000826

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:

0.0000295

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.0000608

AC:

AN:

246536

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133534

show subpopulations

Gnomad AFR exome

AF:

0.000627

Gnomad AMR exome

AF:

0.0000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.000334

GnomAD4 exome

AF:

0.0000470

AC:

AN:

1445452

Hom.:

Cov.:

AF XY:

0.0000389

AC XY:

AN XY:

719046

show subpopulations

Gnomad4 AFR exome

AF:

0.000638

Gnomad4 AMR exome

AF:

0.0000460

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000595

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000127

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.000251

AC:

AN:

151326

Hom.:

Cov.:

AF XY:

0.000284

AC XY:

AN XY:

73868

show subpopulations

Gnomad4 AFR

AF:

0.000848

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:

0.0000295

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000554

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

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

Aug 16, 2021

The c.194C>T (p.S65L) alteration is located in exon 3 (coding exon 3) of the COX16 gene. This alteration results from a C to T substitution at nucleotide position 194, causing the serine (S) at amino acid position 65 to be replaced by a leucine (L). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.;.;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

D;D;.;D;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

2.0

M;.;.;.;.

MutationTaster

Benign

0.99

PROVEAN

Uncertain

-4.0

D;.;.;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.011

D;.;.;.;.

Sift4G

Uncertain

0.019

D;D;.;.;.

Polyphen

1.0

D;.;.;.;.

Vest4

0.57

MVP

0.45

MPC

0.45

ClinPred

0.26

GERP RS

3.6

Varity_R

0.18

gMVP

0.27

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

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