Genetic Variant SYNJ1:c.706-7dupT (chr21-32694317-G-GA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_203446.3(SYNJ1):c.706-7dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00658 in 1,449,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 0 hom. )

Consequence

SYNJ1
NM_203446.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65

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]

SYNJ1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 21-32694317-G-GA is Benign according to our data. Variant chr21-32694317-G-GA is described in ClinVar as [Benign]. Clinvar id is 544582.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000319 (48/150248) while in subpopulation EAS AF= 0.00642 (33/5140). AF 95% confidence interval is 0.0047. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNJ1	NM_203446.3 link	c.706-7dupT		splice_region_variant, intron_variant	Intron 5 of 32	ENST00000674351.1	NP_982271.3	O43426-2C9JFZ1Q05CZ1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1 link	c.706-7_706-6insT		splice_region_variant, intron_variant	Intron 5 of 32		NM_203446.3	ENSP00000501530.1		O43426-2

Frequencies

GnomAD3 genomes

AF:

0.000320

AC:

AN:

150140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00641

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000201

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00731

AC:

9496

AN:

1299550

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

4653

AN XY:

644358

show subpopulations

Gnomad4 AFR exome

AF:

0.00792

Gnomad4 AMR exome

AF:

0.00770

Gnomad4 ASJ exome

AF:

0.00731

Gnomad4 EAS exome

AF:

0.0166

Gnomad4 SAS exome

AF:

0.00988

Gnomad4 FIN exome

AF:

0.00438

Gnomad4 NFE exome

AF:

0.00698

Gnomad4 OTH exome

AF:

0.00693

GnomAD4 genome

AF:

0.000319

AC:

AN:

150248

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

AN XY:

73244

show subpopulations

Gnomad4 AFR

AF:

0.000244

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00642

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000201

Gnomad4 NFE

AF:

0.0000445

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000321

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Nov 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

21-32694317-GAA-GAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over