chr3-63615300-C-T

Variant summary

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

The NM_001130003.2(SYNPR):​c.677C>T​(p.Ser226Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000378 in 1,613,678 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: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SYNPR
NM_001130003.2 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.10
Variant links:
Genes affected
SYNPR (HGNC:16507): (synaptoporin) Predicted to be located in neuron projection and synaptic vesicle. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. Predicted to be integral component of synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11512944).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SYNPRNM_001130003.2 linkuse as main transcriptc.677C>T p.Ser226Leu missense_variant 6/6 ENST00000478300.6 NP_001123475.1
SYNPRNM_144642.5 linkuse as main transcriptc.617C>T p.Ser206Leu missense_variant 5/5 NP_653243.1
SYNPRXM_017005731.1 linkuse as main transcriptc.725C>T p.Ser242Leu missense_variant 6/6 XP_016861220.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYNPRENST00000478300.6 linkuse as main transcriptc.677C>T p.Ser226Leu missense_variant 6/61 NM_001130003.2 ENSP00000418994 P1Q8TBG9-2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152120
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000643
AC:
16
AN:
248824
Hom.:
0
AF XY:
0.0000741
AC XY:
10
AN XY:
135010
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000223
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000929
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461558
Hom.:
0
Cov.:
31
AF XY:
0.0000316
AC XY:
23
AN XY:
727054
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.000112
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152120
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000772
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.000267
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000331
AC:
4
EpiCase
AF:
0.000109
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 GeneticsJun 17, 2024The c.677C>T (p.S226L) alteration is located in exon 6 (coding exon 6) of the SYNPR gene. This alteration results from a C to T substitution at nucleotide position 677, causing the serine (S) at amino acid position 226 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
Benign
0.23
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T;T;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.19
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.97
D;D;D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
.;M;.;.
MutationTaster
Benign
0.99
D;D;D;D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Benign
0.075
Sift
Uncertain
0.0080
D;D;T;D
Sift4G
Uncertain
0.044
D;D;D;T
Polyphen
0.33, 0.48
.;B;P;.
Vest4
0.27
MVP
0.048
MPC
0.12
ClinPred
0.093
T
GERP RS
5.3
Varity_R
0.17
gMVP
0.42

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: rs372110680; hg19: chr3-63600976; COSMIC: COSV55721932; COSMIC: COSV55721932; API