NM_004711.5:c.99+1557T>A

Variant names:

• chr22-39351666-T-A
• rs909685
• NM_004711.5:c.99+1557T>A

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+1557T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,188 control chromosomes in the GnomAD database, including 11,487 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 0.37 (11487 hom., cov: 34)
• Consequence: SYNGR1 NM_004711.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 71 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 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+1557T>A		intron	N/A	NP_004702.2
	SYNGR1	NM_145731.4		c.99+1557T>A		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+1557T>A		intron	N/A	ENSP00000332287.5	O43759-1
	SYNGR1	ENST00000318801.8	TSL:1	c.99+1557T>A		intron	N/A	ENSP00000318845.4	O43759-2
	SYNGR1	ENST00000892373.1		c.99+1557T>A		intron	N/A	ENSP00000562432.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56913 AN: 152072 Hom.: 11482 Cov.: 34

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.374 AC: 56949 AN: 152188 Hom.: 11487 Cov.: 34 AF XY: 0.380 AC XY: 28235 AN XY: 74392

African (AFR) AF: 0.440 AC: 18258 AN: 41524

American (AMR) AF: 0.421 AC: 6433 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 988 AN: 3468

East Asian (EAS) AF: 0.787 AC: 4063 AN: 5162

South Asian (SAS) AF: 0.481 AC: 2321 AN: 4824

European-Finnish (FIN) AF: 0.330 AC: 3503 AN: 10610

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20326 AN: 67994

Other (OTH) AF: 0.369 AC: 777 AN: 2108

Alfa AF: 0.209 Hom.: 454

Bravo AF: 0.383

Asia WGS AF: 0.601 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.44
DANN	Benign	0.59
PhyloP100		-2.4
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: rs909685; hg19: chr22-39747671;