chr16-1991999-C-T

Variant names:

• chr16-1991999-C-T
• rs1486707673
• NM_004209.6:c.125C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004209.6(SYNGR3):​c.125C>T​(p.Pro42Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000693 in 1,442,518 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SYNGR3 NM_004209.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.79
• Publications: 1 publications found

Genes affected

SYNGR3 (HGNC:11501): (synaptogyrin 3) This gene encodes an integral membrane protein. The exact function of this protein is unclear, but studies of a similar murine protein suggest that it is a synaptic vesicle protein that also interacts with the dopamine transporter. The gene product belongs to the synaptogyrin gene family. [provided by RefSeq, Dec 2010]

ENSG00000299741 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2895877).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004209.6. 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
	SYNGR3	NM_004209.6	MANE Select	c.125C>T	p.Pro42Leu	missense	Exon 2 of 4	NP_004200.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNGR3	ENST00000248121.7	TSL:1 MANE Select	c.125C>T	p.Pro42Leu	missense	Exon 2 of 4	ENSP00000248121.2	O43761
	SYNGR3	ENST00000873156.1		c.125C>T	p.Pro42Leu	missense	Exon 2 of 4	ENSP00000543215.1
	SYNGR3	ENST00000568896.1	TSL:5	c.245C>T	p.Pro82Leu	missense	Exon 3 of 4	ENSP00000454756.1	H3BNA6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 211274 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442518 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 716136

African (AFR) AF: 0.00 AC: 0 AN: 32336

American (AMR) AF: 0.00 AC: 0 AN: 43056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25678

East Asian (EAS) AF: 0.00 AC: 0 AN: 38396

South Asian (SAS) AF: 0.00 AC: 0 AN: 84098

European-Finnish (FIN) AF: 0.0000198 AC: 1 AN: 50406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104596

Other (OTH) AF: 0.00 AC: 0 AN: 59504

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.086
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.8
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.063
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.036	D
Polyphen		0.10	B
Vest4		0.51
MutPred		0.61		Gain of catalytic residue at P42 (P = 0.0123)
MVP		0.29
MPC		0.69
ClinPred		0.88	D
GERP RS		4.5
Varity_R		0.33
gMVP		0.65

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: rs1486707673; hg19: chr16-2042000;