chr22-39381844-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004711.5(SYNGR1):ā€‹c.632G>Cā€‹(p.Gly211Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000036 in 1,612,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G211V) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 33)
Exomes š‘“: 0.000038 ( 0 hom. )

Consequence

SYNGR1
NM_004711.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.038630247).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SYNGR1NM_004711.5 linkuse as main transcriptc.632G>C p.Gly211Ala missense_variant 4/4 ENST00000328933.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SYNGR1ENST00000328933.10 linkuse as main transcriptc.632G>C p.Gly211Ala missense_variant 4/41 NM_004711.5 P1O43759-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152114
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000683
AC:
17
AN:
249034
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135258
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00120
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000357
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000377
AC:
55
AN:
1460688
Hom.:
0
Cov.:
35
AF XY:
0.0000413
AC XY:
30
AN XY:
726680
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00165
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152114
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000225
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000742
AC:
9
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 16, 2023The c.632G>C (p.G211A) alteration is located in exon 4 (coding exon 4) of the SYNGR1 gene. This alteration results from a G to C substitution at nucleotide position 632, causing the glycine (G) at amino acid position 211 to be replaced by an alanine (A). 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
0.090
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Benign
0.31
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.63
T
M_CAP
Benign
0.055
D
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.065
N
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.056
Sift
Benign
0.77
T
Sift4G
Benign
0.58
T
Polyphen
0.13
B
Vest4
0.17
MutPred
0.18
Loss of catalytic residue at P207 (P = 0.0722);
MVP
0.23
MPC
0.36
ClinPred
0.045
T
GERP RS
3.3
Varity_R
0.060
gMVP
0.53

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: rs150311775; hg19: chr22-39777849; COSMIC: COSV105194125; COSMIC: COSV105194125; API