rs7279487

Positions:

• chr21-32629514-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNJ1	NM_203446.3	c.*2291A>G		3_prime_UTR_variant	33/33	ENST00000674351.1	NP_982271.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNJ1	ENST00000674351.1	c.*2291A>G		3_prime_UTR_variant	33/33		NM_203446.3	ENSP00000501530

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

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0928

Gnomad4 EAS AF: 0.0470

Gnomad4 SAS AF: 0.0781

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.133

Alfa AF: 0.139 Hom.: 945

Bravo AF: 0.124

Asia WGS AF: 0.0520 AC: 181 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	5.3
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7279487; hg19: chr21-34001824;