14-70329183-C-A

Variant names:

• chr14-70329183-C-A
• rs372378281
• NM_016468.7:c.195G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016468.7(COX16):​c.195G>T​(p.Ser65Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,437,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S65S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: COX16 NM_016468.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=-0.547 with no splicing effect.

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.195G>T	p.Ser65Ser	synonymous	Exon 3 of 4	NP_057552.1	Q9P0S2
	SYNJ2BP-COX16	NM_001202547.2		c.450G>T	p.Ser150Ser	synonymous	Exon 5 of 6	NP_001189476.1
	SYNJ2BP-COX16	NM_001202548.2		c.423G>T	p.Ser141Ser	synonymous	Exon 5 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.195G>T	p.Ser65Ser	synonymous	Exon 3 of 4	ENSP00000374562.5	Q9P0S2
	SYNJ2BP-COX16	ENST00000621525.4	TSL:2	c.423G>T	p.Ser141Ser	synonymous	Exon 5 of 6	ENSP00000482133.1	A0A087WYV9
	SYNJ2BP-COX16	ENST00000617124.4	TSL:2	c.351G>T	p.Ser117Ser	synonymous	Exon 4 of 5	ENSP00000484161.1	A0A087X1F5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1437938 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 715060

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32696

American (AMR) AF: 0.00 AC: 0 AN: 43204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 38098

South Asian (SAS) AF: 0.00 AC: 0 AN: 84862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096984

Other (OTH) AF: 0.00 AC: 0 AN: 58914

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.4
DANN	Benign	0.60
PhyloP100		-0.55

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

Other links and lift over

dbSNP: rs372378281; hg19: chr14-70795900;