22-39350070-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_004711.5(SYNGR1):​c.60G>T​(p.Leu20Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,316,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L20L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: SYNGR1 NM_004711.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=3.2 with no splicing effect.

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

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1316668 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 654024

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

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: 0.0000221 AC: 1 AN: 45296

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1029258

Other (OTH) AF: 0.00 AC: 0 AN: 51628

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		3.2
PromoterAI		-0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs200345991; hg19: chr22-39746075;