Genetic Variant SYCE3:p.Arg50His (chr22-50551363-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001123225.3(SYCE3):c.149G>A(p.Arg50His) variant causes a missense change. The variant allele was found at a frequency of 0.00000967 in 1,550,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

SYCE3
NM_001123225.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

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 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
SYCE3	NM_001123225.3 link	c.149G>A	p.Arg50His	missense_variant	Exon 3 of 3	ENST00000406915.4	NP_001116697.1	A1L190
SYCE3	XM_024452261.2 link	c.149G>A	p.Arg50His	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.149G>A	p.Arg50His	missense_variant	Exon 3 of 3	2	NM_001123225.3	ENSP00000385480.3		A1L190
SYCE3	ENST00000402753.1 link	c.149G>A	p.Arg50His	missense_variant	Exon 2 of 2	1		ENSP00000385122.1		A1L190

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000390

AC:

AN:

153680

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

81610

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1398688

Hom.:

Cov.:

AF XY:

0.00000870

AC XY:

AN XY:

689886

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000168

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:

0.00000649

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.149G>A (p.R50H) alteration is located in exon 3 (coding exon 2) of the SYCE3 gene. This alteration results from a G to A substitution at nucleotide position 149, causing the arginine (R) at amino acid position 50 to be replaced by a histidine (H). 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

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

T;T

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

.;T

M_CAP

Uncertain

0.098

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.30

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

1.0

D;D

Vest4

0.69

MutPred

0.41

Loss of MoRF binding (P = 0.0166);Loss of MoRF binding (P = 0.0166);

MVP

0.40

ClinPred

0.80

GERP RS

6.0

Varity_R

0.31

gMVP

0.83

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