Genetic Variant NM_001123225.3:c.199G>A (chr22-50551313-C-T) – ACMG Classification: Benign (-10 pts)

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

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]

SYCE3 links:

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
SYCE3	NM_001123225.3 link	c.199G>A	p.Val67Ile	missense_variant	Exon 3 of 3	ENST00000406915.4	NP_001116697.1	A1L190
SYCE3	XM_024452261.2 link	c.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
SYCE3	ENST00000406915.4 link	c.199G>A	p.Val67Ile	missense_variant	Exon 3 of 3	2	NM_001123225.3	ENSP00000385480.3		A1L190
SYCE3	ENST00000402753.1 link	c.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.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00352

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00660

AC:

ExAC

AF:

0.00357

AC:

Asia WGS

AF:

0.000866

AC:

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

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.081

T;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0058

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.31

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over