22-50551313-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001123225.3(SYCE3):​c.199G>A​(p.Val67Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,551,270 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 1 hom., cov: 33)
Exomes 𝑓: 0.0063 ( 46 hom. )

Consequence

SYCE3
NM_001123225.3 missense

Scores

18

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47
Variant links:
Genes affected
SYCE3 (HGNC:35245): (synaptonemal complex central element protein 3) Predicted to be involved in reciprocal meiotic recombination; spermatogenesis; and synaptonemal complex assembly. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in chromosome and nucleus. Predicted to be active in central element. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00575307).
BP6
Variant 22-50551313-C-T is Benign according to our data. Variant chr22-50551313-C-T is described in ClinVar as [Benign]. Clinvar id is 2653406.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 46 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SYCE3NM_001123225.3 linkc.199G>A p.Val67Ile missense_variant Exon 3 of 3 ENST00000406915.4 NP_001116697.1 A1L190
SYCE3XM_024452261.2 linkc.199G>A p.Val67Ile missense_variant Exon 3 of 3 XP_024308029.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SYCE3ENST00000406915.4 linkc.199G>A p.Val67Ile missense_variant Exon 3 of 3 2 NM_001123225.3 ENSP00000385480.3 A1L190
SYCE3ENST00000402753.1 linkc.199G>A p.Val67Ile missense_variant Exon 2 of 2 1 ENSP00000385122.1 A1L190

Frequencies

GnomAD3 genomes
AF:
0.00467
AC:
710
AN:
152152
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00137
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.0135
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00689
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00467
AC:
719
AN:
154020
Hom.:
4
AF XY:
0.00454
AC XY:
371
AN XY:
81744
show subpopulations
Gnomad AFR exome
AF:
0.000757
Gnomad AMR exome
AF:
0.00109
Gnomad ASJ exome
AF:
0.00565
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000834
Gnomad FIN exome
AF:
0.0121
Gnomad NFE exome
AF:
0.00691
Gnomad OTH exome
AF:
0.00506
GnomAD4 exome
AF:
0.00628
AC:
8784
AN:
1399000
Hom.:
46
Cov.:
31
AF XY:
0.00611
AC XY:
4214
AN XY:
690022
show subpopulations
Gnomad4 AFR exome
AF:
0.00101
Gnomad4 AMR exome
AF:
0.00118
Gnomad4 ASJ exome
AF:
0.00635
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000833
Gnomad4 FIN exome
AF:
0.0123
Gnomad4 NFE exome
AF:
0.00701
Gnomad4 OTH exome
AF:
0.00547
GnomAD4 genome
AF:
0.00466
AC:
709
AN:
152270
Hom.:
1
Cov.:
33
AF XY:
0.00469
AC XY:
349
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.00120
Gnomad4 AMR
AF:
0.00137
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.0135
Gnomad4 NFE
AF:
0.00689
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00590
Hom.:
4
Bravo
AF:
0.00352
TwinsUK
AF:
0.00485
AC:
18
ALSPAC
AF:
0.00882
AC:
34
ESP6500AA
AF:
0.00289
AC:
4
ESP6500EA
AF:
0.00660
AC:
21
ExAC
AF:
0.00357
AC:
94
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Jul 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

SYCE3: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
21
DANN
Benign
0.93
DEOGEN2
Benign
0.081
T;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.69
.;T
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.0058
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.56
N;N
REVEL
Benign
0.014
Sift
Benign
0.10
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.079
B;B
Vest4
0.15
MVP
0.081
ClinPred
0.0074
T
GERP RS
2.4
Varity_R
0.033
gMVP
0.43

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: rs55829948; hg19: chr22-50989742; API