rs61755328

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_203446.3(SYNJ1):​c.43C>A​(p.Pro15Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SYNJ1
NM_203446.3 missense

Scores

5
11
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.43
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.837

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYNJ1NM_203446.3 linkuse as main transcriptc.43C>A p.Pro15Thr missense_variant 2/33 ENST00000674351.1 NP_982271.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYNJ1ENST00000674351.1 linkuse as main transcriptc.43C>A p.Pro15Thr missense_variant 2/33 NM_203446.3 ENSP00000501530 O43426-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461876
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
.;T;.;T;T;.;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.97
D;D;D;D;D;D;D
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.84
D;D;D;D;D;D;D
MetaSVM
Pathogenic
0.95
D
MutationAssessor
Uncertain
2.3
M;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.1
D;D;.;D;D;D;D
REVEL
Pathogenic
0.79
Sift
Uncertain
0.014
D;D;.;D;D;D;D
Sift4G
Uncertain
0.034
D;D;D;D;D;.;.
Polyphen
1.0
D;.;.;P;.;.;.
Vest4
0.63
MutPred
0.43
Loss of glycosylation at P15 (P = 0.0283);Loss of glycosylation at P15 (P = 0.0283);Loss of glycosylation at P15 (P = 0.0283);.;.;Loss of glycosylation at P15 (P = 0.0283);Loss of glycosylation at P15 (P = 0.0283);
MVP
0.92
MPC
1.6
ClinPred
0.99
D
GERP RS
4.5
gMVP
0.57

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: rs61755328; hg19: chr21-34099164; API