3-63615293-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001130003.2(SYNPR):​c.670C>T​(p.His224Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SYNPR
NM_001130003.2 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.97
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYNPRNM_001130003.2 linkc.670C>T p.His224Tyr missense_variant Exon 6 of 6 ENST00000478300.6 NP_001123475.1 Q8TBG9-2
SYNPRNM_144642.5 linkc.610C>T p.His204Tyr missense_variant Exon 5 of 5 NP_653243.1 Q8TBG9-1
SYNPRXM_017005731.1 linkc.718C>T p.His240Tyr missense_variant Exon 6 of 6 XP_016861220.1
SYNPRXM_017005732.3 linkc.*4751C>T downstream_gene_variant XP_016861221.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYNPRENST00000478300.6 linkc.670C>T p.His224Tyr missense_variant Exon 6 of 6 1 NM_001130003.2 ENSP00000418994.1 Q8TBG9-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461428
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726992
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:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
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
Nov 11, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.670C>T (p.H224Y) 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 670, causing the histidine (H) at amino acid position 224 to be replaced by a tyrosine (Y). 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
0.43
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
.;T;T;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.85
T;D;T;D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.74
D;D;D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
.;M;.;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.0
D;D;D;N
REVEL
Benign
0.19
Sift
Benign
0.13
T;T;T;D
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.98
.;D;D;.
Vest4
0.74
MutPred
0.55
.;.;Loss of disorder (P = 0.055);.;
MVP
0.081
MPC
0.11
ClinPred
0.95
D
GERP RS
5.3
Varity_R
0.25
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-63600969; API