chr21-32631035-G-A

Position:

• chr21-32631035-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000433931.7(SYNJ1):​c.4799C>T​(p.Ala1600Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1600T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYNJ1 ENST00000433931.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

Genes affected

SYNJ1 (HGNC:11503): (synaptojanin 1) This gene encodes a phosphoinositide phosphatase that regulates levels of membrane phosphatidylinositol-4,5-bisphosphate. As such, expression of this enzyme may affect synaptic transmission and membrane trafficking. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20707527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3	c.*770C>T		3_prime_UTR_variant	33/33	ENST00000674351.1	NP_982271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1	c.*770C>T		3_prime_UTR_variant	33/33		NM_203446.3	ENSP00000501530

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	14
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.61	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.65	.;N
REVEL	Benign	0.23
Sift	Uncertain	0.010	.;D
Sift4G	Benign	0.34	T;T
Vest4		0.12
MVP		0.81
MPC		0.23
ClinPred		0.36	T
GERP RS		5.9
gMVP		0.38

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: rs2039298283; hg19: chr21-34003345;