NM_203446.3:c.*2291A>G

Variant names:

• chr21-32629514-T-C
• rs7279487
• NM_203446.3:c.*2291A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_203446.3(SYNJ1):​c.*2291A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,706 control chromosomes in the GnomAD database, including 1,290 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1287 hom., cov: 33)
  • Exomes 𝑓: 0.12 (3 hom.)
• Consequence: SYNJ1 NM_203446.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 9 publications found

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]

SYNJ1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 53

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• early-onset Parkinson disease 20

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• atypical juvenile parkinsonism

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• young-onset Parkinson disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ1	NM_203446.3	MANE Select	c.*2291A>G		3_prime_UTR	Exon 33 of 33	NP_982271.3
	SYNJ1	NM_003895.4		c.*1481A>G		3_prime_UTR	Exon 32 of 32	NP_003886.3
	SYNJ1	NM_001160306.2		c.*1481A>G		3_prime_UTR	Exon 28 of 28	NP_001153778.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ1	ENST00000674351.1	MANE Select	c.*2291A>G		3_prime_UTR	Exon 33 of 33	ENSP00000501530.1
	SYNJ1	ENST00000433931.7	TSL:1	c.*1481A>G		3_prime_UTR	Exon 32 of 32	ENSP00000409667.2
	SYNJ1	ENST00000630077.3	TSL:1	c.*1481A>G		3_prime_UTR	Exon 28 of 28	ENSP00000487560.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19271 AN: 152156 Hom.: 1286 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.0471

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.135

GnomAD4 exome AF: 0.120 AC: 52 AN: 432 Hom.: 3 Cov.: 0 AF XY: 0.142 AC XY: 37 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.122 AC: 52 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.127 AC: 19288 AN: 152274 Hom.: 1287 Cov.: 33 AF XY: 0.123 AC XY: 9186 AN XY: 74472

African (AFR) AF: 0.119 AC: 4931 AN: 41536

American (AMR) AF: 0.118 AC: 1806 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3468

East Asian (EAS) AF: 0.0470 AC: 244 AN: 5190

South Asian (SAS) AF: 0.0781 AC: 377 AN: 4830

European-Finnish (FIN) AF: 0.117 AC: 1246 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9980 AN: 68016

Other (OTH) AF: 0.133 AC: 281 AN: 2110

Alfa AF: 0.138 Hom.: 2977

Bravo AF: 0.124

Asia WGS AF: 0.0520 AC: 181 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7279487; hg19: chr21-34001824;