22-39355246-G-C

Position:

• chr22-39355246-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNGR1	NM_004711.5	c.99+5137G>C		intron_variant		ENST00000328933.10	NP_004702.2
SYNGR1	NM_145731.4	c.99+5137G>C		intron_variant			NP_663783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNGR1	ENST00000328933.10	c.99+5137G>C		intron_variant		1	NM_004711.5	ENSP00000332287	P1

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

Gnomad4 AFR AF: 0.0657

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.778

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.244

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.74

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: rs715505; hg19: chr22-39751251;