rs10143078

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ2BP	NM_018373.3	c.64+2128T>G		intron_variant	Intron 1 of 3	ENST00000256366.6	NP_060843.2
SYNJ2BP-COX16	NM_001202547.2	c.64+2128T>G		intron_variant	Intron 1 of 5		NP_001189476.1
SYNJ2BP-COX16	NM_001202548.2	c.64+2128T>G		intron_variant	Intron 1 of 5		NP_001189477.1
SYNJ2BP-COX16	NM_001202549.2	c.64+2128T>G		intron_variant	Intron 1 of 4		NP_001189478.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ2BP	ENST00000256366.6	c.64+2128T>G		intron_variant	Intron 1 of 3	1	NM_018373.3	ENSP00000256366.4
SYNJ2BP-COX16	ENST00000621525.4	c.64+2128T>G		intron_variant	Intron 1 of 5	2		ENSP00000482133.1

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

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.0432

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.0803

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.0312

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0484 Hom.: 59

Bravo AF: 0.0714

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs10143078; hg19: chr14-70881489;