NM_004209.6:c.125C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79
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 1 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNGR3NM_004209.6 linkc.125C>T p.Pro42Leu missense_variant Exon 2 of 4 ENST00000248121.7 NP_004200.2 O43761

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNGR3ENST00000248121.7 linkc.125C>T p.Pro42Leu missense_variant Exon 2 of 4 1 NM_004209.6 ENSP00000248121.2 O43761
SYNGR3ENST00000568896.1 linkc.245C>T p.Pro82Leu missense_variant Exon 3 of 4 5 ENSP00000454756.1 H3BNA6
SYNGR3ENST00000563869.1 linkc.57C>T p.Ala19Ala synonymous_variant Exon 2 of 4 2 ENSP00000455344.1 H3BPJ5
SYNGR3ENST00000562045 linkc.-141C>T 5_prime_UTR_variant Exon 1 of 3 2 ENSP00000455577.1 H3BQ28

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.93e-7
AC:
1
AN:
1442518
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
716136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000198
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 30, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.125C>T (p.P42L) alteration is located in exon 2 (coding exon 2) of the SYNGR3 gene. This alteration results from a C to T substitution at nucleotide position 125, causing the proline (P) at amino acid position 42 to be replaced by a leucine (L). 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
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;.;T
Eigen
Benign
-0.076
Eigen_PC
Benign
0.086
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N;.;.
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-1.3
N;.;N
REVEL
Benign
0.063
Sift
Uncertain
0.026
D;.;T
Sift4G
Uncertain
0.036
D;D;T
Polyphen
0.10
B;.;.
Vest4
0.51
MutPred
0.61
Gain of catalytic residue at P42 (P = 0.0123);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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1486707673; hg19: chr16-2042000; API