22-39352849-A-G

Variant names:

• chr22-39352849-A-G
• rs137699
• NM_004711.5:c.99+2740A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

SYNGR1 Gene-Disease associations (from GenCC):

• bipolar disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004711.5. 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
	SYNGR1	NM_004711.5	MANE Select	c.99+2740A>G		intron	N/A	NP_004702.2
	SYNGR1	NM_145731.4		c.99+2740A>G		intron	N/A	NP_663783.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNGR1	ENST00000328933.10	TSL:1 MANE Select	c.99+2740A>G		intron	N/A	ENSP00000332287.5
	SYNGR1	ENST00000318801.8	TSL:1	c.99+2740A>G		intron	N/A	ENSP00000318845.4
	SYNGR1	ENST00000406293.7	TSL:2	c.99+2740A>G		intron	N/A	ENSP00000385447.3

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

African (AFR) AF: 0.256 AC: 10605 AN: 41466

American (AMR) AF: 0.729 AC: 11137 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2361 AN: 3466

East Asian (EAS) AF: 0.861 AC: 4457 AN: 5178

South Asian (SAS) AF: 0.732 AC: 3526 AN: 4814

European-Finnish (FIN) AF: 0.685 AC: 7253 AN: 10582

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45509 AN: 67952

Other (OTH) AF: 0.594 AC: 1254 AN: 2112

Alfa AF: 0.618 Hom.: 53479

Bravo AF: 0.559

Asia WGS AF: 0.736 AC: 2558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0040
DANN	Benign	0.44
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs137699; hg19: chr22-39748854;