22-39355246-G-C

Variant names:

• chr22-39355246-G-C
• rs715505
• NM_004711.5:c.99+5137G>C

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+5137G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,186 control chromosomes in the GnomAD database, including 5,334 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 0.22 (5334 hom., cov: 32)
• Consequence: SYNGR1 NM_004711.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNGR1	NM_004711.5	MANE Select	c.99+5137G>C		intron	N/A	NP_004702.2
	SYNGR1	NM_145731.4		c.99+5137G>C		intron	N/A	NP_663783.1	O43759-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNGR1	ENST00000328933.10	TSL:1 MANE Select	c.99+5137G>C		intron	N/A	ENSP00000332287.5	O43759-1
	SYNGR1	ENST00000318801.8	TSL:1	c.99+5137G>C		intron	N/A	ENSP00000318845.4	O43759-2
	SYNGR1	ENST00000892373.1		c.99+5137G>C		intron	N/A	ENSP00000562432.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33902 AN: 152068 Hom.: 5335 Cov.: 32

Gnomad AFR AF: 0.0658

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.223 AC: 33913 AN: 152186 Hom.: 5334 Cov.: 32 AF XY: 0.234 AC XY: 17403 AN XY: 74404

African (AFR) AF: 0.0657 AC: 2730 AN: 41554

American (AMR) AF: 0.343 AC: 5251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.778 AC: 4022 AN: 5172

South Asian (SAS) AF: 0.349 AC: 1681 AN: 4816

European-Finnish (FIN) AF: 0.304 AC: 3224 AN: 10602

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15537 AN: 67970

Other (OTH) AF: 0.244 AC: 515 AN: 2112

Alfa AF: 0.222 Hom.: 554

Bravo AF: 0.221

Asia WGS AF: 0.518 AC: 1799 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		0.31
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: rs715505; hg19: chr22-39751251;