Variant 14-70373031-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018373.3(SYNJ2BP):c.398T>C(p.Val133Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SYNJ2BP
NM_018373.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

Variant links:

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 links:

SYNJ2BP-COX16 (HGNC:):

SYNJ2BP-COX16 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.34983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SYNJ2BP	NM_018373.3 linkuse as main transcript	c.398T>C	p.Val133Ala	missense_variant	4/4	ENST00000256366.6	NP_060843.2
SYNJ2BP-COX16	NM_001202549.2 linkuse as main transcript	c.297+2645T>C		intron_variant			NP_001189478.1
SYNJ2BP-COX16	NM_001202547.2 linkuse as main transcript	c.396+2T>C		splice_donor_variant			NP_001189476.1
SYNJ2BP-COX16	NM_001202548.2 linkuse as main transcript	c.297+2645T>C		intron_variant			NP_001189477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SYNJ2BP	ENST00000256366.6 linkuse as main transcript	c.398T>C	p.Val133Ala	missense_variant	4/4	1	NM_018373.3	ENSP00000256366	P1
SYNJ2BP	ENST00000554216.1 linkuse as main transcript	n.359T>C		non_coding_transcript_exon_variant	3/3	1
COX16	ENST00000555276.5 linkuse as main transcript	c.-72-30302T>C		intron_variant		2		ENSP00000480746

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152170

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250560

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000443

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000581

Hom.:

Bravo

AF:

0.0000302

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.398T>C (p.V133A) alteration is located in exon 4 (coding exon 4) of the SYNJ2BP gene. This alteration results from a T to C substitution at nucleotide position 398, causing the valine (V) at amino acid position 133 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.088

M_CAP

Benign

0.0027

MutationTaster

Benign

1.0

ClinPred

0.57

GERP RS

4.3

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over