rs200345991

Variant names:

• chr22-39350070-G-A
• rs200345991
• NM_004711.5:c.60G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-39350070-G-A
• chr22-39350070-G-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_004711.5(SYNGR1):​c.60G>A​(p.Leu20Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,467,272 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: SYNGR1 NM_004711.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.21
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 22-39350070-G-A is Benign according to our data. Variant chr22-39350070-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2653148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=3.2 with no splicing effect.
• BS2: High AC in GnomAd4 at 18 AD,Unknown gene.

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.60G>A	p.Leu20Leu	synonymous	Exon 1 of 4	NP_004702.2
	SYNGR1	NM_145731.4		c.60G>A	p.Leu20Leu	synonymous	Exon 1 of 4	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.60G>A	p.Leu20Leu	synonymous	Exon 1 of 4	ENSP00000332287.5	O43759-1
	SYNGR1	ENST00000318801.8	TSL:1	c.60G>A	p.Leu20Leu	synonymous	Exon 1 of 4	ENSP00000318845.4	O43759-2
	SYNGR1	ENST00000892373.1		c.60G>A	p.Leu20Leu	synonymous	Exon 1 of 5	ENSP00000562432.1

Frequencies

GnomAD3 genomes AF: 0.000120 AC: 18 AN: 150608 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000264 AC: 45 AN: 170776 AF XY: 0.000209

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.0000918

Gnomad OTH exome AF: 0.000261

GnomAD4 exome AF: 0.000125 AC: 165 AN: 1316664 Hom.: 0 Cov.: 30 AF XY: 0.000119 AC XY: 78 AN XY: 654022

African (AFR) AF: 0.00 AC: 0 AN: 26914

American (AMR) AF: 0.00 AC: 0 AN: 34596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21154

East Asian (EAS) AF: 0.00 AC: 0 AN: 27790

South Asian (SAS) AF: 0.00 AC: 0 AN: 74918

European-Finnish (FIN) AF: 0.00124 AC: 56 AN: 45294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5114

European-Non Finnish (NFE) AF: 0.0000972 AC: 100 AN: 1029256

Other (OTH) AF: 0.000174 AC: 9 AN: 51628

GnomAD4 genome AF: 0.000120 AC: 18 AN: 150608 Hom.: 0 Cov.: 30 AF XY: 0.000123 AC XY: 9 AN XY: 73466

African (AFR) AF: 0.00 AC: 0 AN: 41246

American (AMR) AF: 0.00 AC: 0 AN: 15102

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00110 AC: 11 AN: 10036

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

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67480

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.0000751 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	15
DANN	Uncertain	0.98
PhyloP100		3.2
PromoterAI		-0.0020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200345991; hg19: chr22-39746075;