dbSNP rs573618970: COX16:p.Arg34Pro (chr14-70342698-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_016468.7(COX16):c.101G>C(p.Arg34Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,612,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R34H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

COX16
NM_016468.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.44

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: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]

SYNJ2BP-COX16 links:

ENSG00000259033 (HGNC:):

ENSG00000259033 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COX16	NM_016468.7 link	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 4	ENST00000389912.7	NP_057552.1	Q9P0S2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COX16	ENST00000389912.7 link	c.101G>C	p.Arg34Pro	missense_variant	Exon 2 of 4	1	NM_016468.7	ENSP00000374562.5		Q9P0S2
SYNJ2BP-COX16	ENST00000621525.4 link	c.329G>C	p.Arg110Pro	missense_variant	Exon 4 of 6	2		ENSP00000482133.1		A0A087WYV9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460718

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.0086

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.5

M;.

PROVEAN

Uncertain

-4.0

D;.

REVEL

Benign

0.16

Sift

Uncertain

0.0040

D;.

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;.

Vest4

0.85

MutPred

0.45

Loss of sheet (P = 0.0457);.;

MVP

0.47

MPC

0.82

ClinPred

1.0

GERP RS

5.0

Varity_R

0.84

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over