rs372378281

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr14-70329183-C-T
• chr14-70329183-C-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_016468.7(COX16):​c.195G>A​(p.Ser65Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000661 in 1,588,980 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: COX16 NM_016468.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.547
• Publications: 2 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 14-70329183-C-T is Benign according to our data. Variant chr14-70329183-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3076444.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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>A	p.Ser65Ser	synonymous	Exon 3 of 4	NP_057552.1	Q9P0S2
	SYNJ2BP-COX16	NM_001202547.2		c.450G>A	p.Ser150Ser	synonymous	Exon 5 of 6	NP_001189476.1
	SYNJ2BP-COX16	NM_001202548.2		c.423G>A	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>A	p.Ser65Ser	synonymous	Exon 3 of 4	ENSP00000374562.5	Q9P0S2
	SYNJ2BP-COX16	ENST00000621525.4	TSL:2	c.423G>A	p.Ser141Ser	synonymous	Exon 5 of 6	ENSP00000482133.1	A0A087WYV9
	SYNJ2BP-COX16	ENST00000617124.4	TSL:2	c.351G>A	p.Ser117Ser	synonymous	Exon 4 of 5	ENSP00000484161.1	A0A087X1F5

Frequencies

GnomAD3 genomes AF: 0.000324 AC: 49 AN: 151046 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00251

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: 0.000481

GnomAD2 exomes AF: 0.0000974 AC: 24 AN: 246380 AF XY: 0.0000375

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.000545

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000446

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000389 AC: 56 AN: 1437934 Hom.: 0 Cov.: 30 AF XY: 0.0000266 AC XY: 19 AN XY: 715058

African (AFR) AF: 0.0000306 AC: 1 AN: 32696

American (AMR) AF: 0.000394 AC: 17 AN: 43202

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

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

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84862

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52376

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

European-Non Finnish (NFE) AF: 0.0000283 AC: 31 AN: 1096982

Other (OTH) AF: 0.0000849 AC: 5 AN: 58914

GnomAD4 genome AF: 0.000324 AC: 49 AN: 151046 Hom.: 0 Cov.: 31 AF XY: 0.000516 AC XY: 38 AN XY: 73714

African (AFR) AF: 0.000194 AC: 8 AN: 41166

American (AMR) AF: 0.00251 AC: 38 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67700

Other (OTH) AF: 0.000481 AC: 1 AN: 2078

Alfa AF: 0.000216 Hom.: 0

Bravo AF: 0.000238

Asia WGS AF: 0.000870 AC: 3 AN: 3464

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.64
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; COSMIC: COSV101112176; COSMIC: COSV101112176;