NM_203446.3:c.-42A>G

Variant names:

• chr21-32727965-T-C
• rs988950141
• NM_203446.3:c.-42A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_203446.3(SYNJ1):​c.-42A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000561 in 1,534,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: SYNJ1 NM_203446.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 0.211
• Publications: 0 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]

PAXBP1-AS1 (HGNC:39603): (PAXBP1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21686718).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ1	NM_203446.3	MANE Select	c.-42A>G		5_prime_UTR	Exon 1 of 33	NP_982271.3	O43426-2
	SYNJ1	NM_003895.4		c.76A>G	p.Arg26Gly	missense	Exon 1 of 32	NP_003886.3
	SYNJ1	NM_001160306.2		c.-151A>G		upstream_gene	N/A	NP_001153778.1	A0A0D9SGJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNJ1	ENST00000674351.1	MANE Select	c.-42A>G		5_prime_UTR	Exon 1 of 33	ENSP00000501530.1	O43426-2
	SYNJ1	ENST00000674308.1		c.-42A>G		5_prime_UTR	Exon 1 of 32	ENSP00000501426.1	O43426-1
	SYNJ1	ENST00000902244.1		c.-151A>G		5_prime_UTR	Exon 1 of 31	ENSP00000572303.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 151942 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000309 AC: 4 AN: 129526 AF XY: 0.0000423

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000623

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000557 AC: 77 AN: 1382114 Hom.: 0 Cov.: 31 AF XY: 0.0000484 AC XY: 33 AN XY: 682116

African (AFR) AF: 0.00 AC: 0 AN: 31192

American (AMR) AF: 0.000112 AC: 4 AN: 35650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25092

East Asian (EAS) AF: 0.00 AC: 0 AN: 35518

South Asian (SAS) AF: 0.00 AC: 0 AN: 79140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4992

European-Non Finnish (NFE) AF: 0.0000649 AC: 70 AN: 1077948

Other (OTH) AF: 0.0000520 AC: 3 AN: 57720

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 151942 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74210

African (AFR) AF: 0.0000242 AC: 1 AN: 41354

American (AMR) AF: 0.000131 AC: 2 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Early-onset Parkinson disease 20;C4479313:Developmental and epileptic encephalopathy, 53 (1)
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.25	T
PhyloP100		0.21
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.25
MutPred		0.28		Gain of methylation at R25 (P = 0.0239)
MVP		0.65
MPC		1.7
ClinPred		0.32	T
GERP RS		3.4
PromoterAI		-0.12	Neutral
gMVP		0.28
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs988950141; hg19: chr21-34100276;