Genetic Variant SYCE3:p.Met59Val (chr22-50551337-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001123225.3(SYCE3):c.175A>G(p.Met59Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000286 in 1,399,050 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: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SYCE3
NM_001123225.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

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:

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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=0.2130315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCE3	NM_001123225.3 link	c.175A>G	p.Met59Val	missense_variant	Exon 3 of 3	ENST00000406915.4	NP_001116697.1	A1L190
SYCE3	XM_024452261.2 link	c.175A>G	p.Met59Val	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.175A>G	p.Met59Val	missense_variant	Exon 3 of 3	2	NM_001123225.3	ENSP00000385480.3		A1L190
SYCE3	ENST00000402753.1 link	c.175A>G	p.Met59Val	missense_variant	Exon 2 of 2	1		ENSP00000385122.1		A1L190

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000649

AC:

AN:

154100

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690044

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:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000382

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175A>G (p.M59V) alteration is located in exon 3 (coding exon 2) of the SYCE3 gene. This alteration results from a A to G substitution at nucleotide position 175, causing the methionine (M) at amino acid position 59 to be replaced by a valine (V). 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

0.24

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.47

T;T

Eigen

Benign

-0.032

Eigen_PC

Benign

0.098

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.99

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.4

D;D

REVEL

Benign

0.20

Sift

Uncertain

0.011

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.23

B;B

Vest4

0.50

MutPred

0.29

Loss of disorder (P = 0.096);Loss of disorder (P = 0.096);

MVP

0.14

ClinPred

0.32

GERP RS

3.8

Varity_R

0.26

gMVP

0.76

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