16-1990166-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004209.6(SYNGR3):​c.64C>T​(p.Arg22Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,263,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SYNGR3
NM_004209.6 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.388
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17694902).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNGR3NM_004209.6 linkc.64C>T p.Arg22Trp missense_variant Exon 1 of 4 ENST00000248121.7 NP_004200.2 O43761

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNGR3ENST00000248121.7 linkc.64C>T p.Arg22Trp missense_variant Exon 1 of 4 1 NM_004209.6 ENSP00000248121.2 O43761

Frequencies

GnomAD3 genomes
AF:
0.0000792
AC:
12
AN:
151550
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00136
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000964
GnomAD4 exome
AF:
0.0000189
AC:
21
AN:
1111744
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
8
AN XY:
530552
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000493
Gnomad4 SAS exome
AF:
0.0000324
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000107
Gnomad4 OTH exome
AF:
0.000134
GnomAD4 genome
AF:
0.0000791
AC:
12
AN:
151658
Hom.:
0
Cov.:
31
AF XY:
0.0000675
AC XY:
5
AN XY:
74076
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00136
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000954
Bravo
AF:
0.0000416

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.64C>T (p.R22W) alteration is located in exon 1 (coding exon 1) of the SYNGR3 gene. This alteration results from a C to T substitution at nucleotide position 64, causing the arginine (R) at amino acid position 22 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
22
DANN
Benign
0.92
DEOGEN2
Benign
0.17
T;.;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.27
N
LIST_S2
Uncertain
0.93
D;D;T
M_CAP
Pathogenic
0.30
D
MetaRNN
Benign
0.18
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;.;.
PrimateAI
Pathogenic
0.93
D
PROVEAN
Uncertain
-4.1
D;.;N
REVEL
Benign
0.093
Sift
Uncertain
0.0020
D;.;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.99
D;.;.
Vest4
0.29
MutPred
0.50
Gain of catalytic residue at A21 (P = 0.0196);Gain of catalytic residue at A21 (P = 0.0196);.;
MVP
0.30
MPC
1.5
ClinPred
0.90
D
GERP RS
-1.3
Varity_R
0.18
gMVP
0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1421865408; hg19: chr16-2040167; API