rs994115947

chr21-32641960-C-Tchr21-32641960-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203446.3(SYNJ1):c.3524G>A(p.Ser1175Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict 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. S1175T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYNJ1 NM_203446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028485239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNJ1	NM_203446.3	c.3524G>A	p.Ser1175Asn	missense_variant	29/33	ENST00000674351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNJ1	ENST00000674351.1	c.3524G>A	p.Ser1175Asn	missense_variant	29/33		NM_203446.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	0.14
Dann	Benign	0.45
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0055	N
LIST_S2	Benign	0.73	T;T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.028	T;T;T;T;T
MetaSVM	Benign	-0.65	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.010	N;N;.;N;N
REVEL	Benign	0.28
Sift	Benign	0.78	T;T;.;T;T
Sift4G	Benign	0.60	T;T;T;T;T
Polyphen		0.0	B;.;.;B;.
Vest4		0.12
MVP		0.52
MPC		0.11
ClinPred		0.032	T
GERP RS		-3.1
gMVP		0.026

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: rs994115947; hg19: chr21-34014270;