rs10143078

Variant names:

• chr14-70414772-A-C
• rs10143078
• NM_018373.3:c.64+2128T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018373.3(SYNJ2BP):​c.64+2128T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 152,264 control chromosomes in the GnomAD database, including 561 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.066 (561 hom., cov: 32)
• Consequence: SYNJ2BP NM_018373.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 6 publications found

Genes affected

SYNJ2BP (HGNC:18955): (synaptojanin 2 binding protein) Predicted to enable type II activin receptor binding activity. Involved in several processes, including negative regulation of endothelial cell migration; negative regulation of sprouting angiogenesis; and regulation of signal transduction. Located in mitochondrion. Is integral component of mitochondrial outer 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]

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 Gene-Disease associations (from GenCC):

• mitochondrial complex IV deficiency, nuclear type 22

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018373.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2BP	NM_018373.3	MANE Select	c.64+2128T>G		intron	N/A	NP_060843.2
	SYNJ2BP-COX16	NM_001202547.2		c.64+2128T>G		intron	N/A	NP_001189476.1
	SYNJ2BP-COX16	NM_001202548.2		c.64+2128T>G		intron	N/A	NP_001189477.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ2BP	ENST00000256366.6	TSL:1 MANE Select	c.64+2128T>G		intron	N/A	ENSP00000256366.4
	SYNJ2BP-COX16	ENST00000621525.4	TSL:2	c.64+2128T>G		intron	N/A	ENSP00000482133.1
	SYNJ2BP	ENST00000554216.1	TSL:1	n.162+2128T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0655 AC: 9970 AN: 152146 Hom.: 560 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0807

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0312

Gnomad OTH AF: 0.0611

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0655 AC: 9975 AN: 152264 Hom.: 561 Cov.: 32 AF XY: 0.0663 AC XY: 4935 AN XY: 74468

African (AFR) AF: 0.145 AC: 6033 AN: 41516

American (AMR) AF: 0.0432 AC: 660 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3472

East Asian (EAS) AF: 0.0803 AC: 417 AN: 5190

South Asian (SAS) AF: 0.0793 AC: 383 AN: 4828

European-Finnish (FIN) AF: 0.00367 AC: 39 AN: 10622

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0312 AC: 2124 AN: 68026

Other (OTH) AF: 0.0610 AC: 129 AN: 2116

Alfa AF: 0.0529 Hom.: 121

Bravo AF: 0.0714

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.36
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs10143078; hg19: chr14-70881489;