chr21-32631012-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003895.4(SYNJ1):​c.4822G>A​(p.Asp1608Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1608Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

SYNJ1
NM_003895.4 missense

Scores

8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.71
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3049235).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNJ1NM_203446.3 linkc.*793G>A 3_prime_UTR_variant Exon 33 of 33 ENST00000674351.1 NP_982271.3 O43426-2C9JFZ1Q05CZ1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNJ1ENST00000674351 linkc.*793G>A 3_prime_UTR_variant Exon 33 of 33 NM_203446.3 ENSP00000501530.1 O43426-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.013
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
.;T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.042
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.63
T
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.78
.;N
REVEL
Benign
0.25
Sift
Uncertain
0.0060
.;D
Sift4G
Uncertain
0.040
D;D
Vest4
0.29
MVP
0.81
MPC
0.37
ClinPred
0.58
D
GERP RS
4.7
gMVP
0.29

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.

Other links and lift over

dbSNP: rs536572904; hg19: chr21-34003322; API