rs137699

Positions:

• chr22-39352849-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004711.5(SYNGR1):​c.99+2740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,060 control chromosomes in the GnomAD database, including 27,786 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 0.57 (27786 hom., cov: 32)
• Consequence: SYNGR1 NM_004711.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

Genes affected

SYNGR1 (HGNC:11498): (synaptogyrin 1) This gene encodes an integral membrane protein associated with presynaptic vesicles in neuronal cells. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it functions in synaptic plasticity without being required for synaptic transmission. The gene product belongs to the synaptogyrin gene family. Three alternatively spliced variants encoding three different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNGR1	NM_004711.5	c.99+2740A>G		intron_variant		ENST00000328933.10	NP_004702.2
SYNGR1	NM_145731.4	c.99+2740A>G		intron_variant			NP_663783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNGR1	ENST00000328933.10	c.99+2740A>G		intron_variant		1	NM_004711.5	ENSP00000332287	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86771 AN: 151942 Hom.: 27781 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.861

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.593

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86788 AN: 152060 Hom.: 27786 Cov.: 32 AF XY: 0.578 AC XY: 42988 AN XY: 74340

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.729

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.594

Alfa AF: 0.648 Hom.: 33233

Bravo AF: 0.559

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0040
DANN	Benign	0.44

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: rs137699; hg19: chr22-39748854;