ENST00000303903.10:c.928C>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000303903.10(SYCE1):c.928C>G(p.Pro310Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,613,770 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 163 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 193 hom. )

Consequence

SYCE1
ENST00000303903.10 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.229

Variant links:

Genes affected

SYCE1 (HGNC:28852): (synaptonemal complex central element protein 1) This gene encodes a member of the synaptonemal complex, which links homologous chromosomes during prophase I of meiosis. The tripartite structure of the complex is highly conserved amongst metazoans. It consists of two lateral elements and a central region formed by transverse elements and a central element. The protein encoded by this gene localizes to the central element and is required for initiation and elongation of the synapsis. Allelic variants of this gene have been associated with premature ovarian failure and spermatogenic failure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

SYCE1 links:

CYP2E1 (HGNC:2631): (cytochrome P450 family 2 subfamily E member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]

CYP2E1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021859705).

BP6

Variant 10-133554319-G-C is Benign according to our data. Variant chr10-133554319-G-C is described in ClinVar as [Benign]. Clinvar id is 775291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCE1	NM_001143763.2 link	c.928C>G	p.Pro310Ala	missense_variant	Exon 13 of 13		NP_001137235.1	Q8N0S2A0A0B4J1R9
SYCE1	NM_130784.4 link	c.820C>G	p.Pro274Ala	missense_variant	Exon 13 of 13		NP_570140.1	Q8N0S2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SYCE1	ENST00000303903.10 link	c.928C>G	p.Pro310Ala	missense_variant	Exon 13 of 13	1	ENSP00000303978.5	A0A0B4J1R9
CYP2E1	ENST00000368520.1 link	n.1359-342G>C		intron_variant	Intron 5 of 5	1
SYCE1	ENST00000368517.7 link	c.820C>G	p.Pro274Ala	missense_variant	Exon 13 of 13	5	ENSP00000357503.3	Q8N0S2-2
SYCE1	ENST00000479535.2 link	n.2061C>G		non_coding_transcript_exon_variant	Exon 11 of 11	5

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3975

AN:

151998

Hom.:

163

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00904

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00699

AC:

1758

AN:

251442

Hom.:

AF XY:

0.00500

AC XY:

680

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0965

Gnomad AMR exome

AF:

0.00419

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00266

AC:

3881

AN:

1461654

Hom.:

193

Cov.:

AF XY:

0.00222

AC XY:

1611

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0949

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.0262

AC:

3981

AN:

152116

Hom.:

163

Cov.:

AF XY:

0.0253

AC XY:

1883

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0916

Gnomad4 AMR

AF:

0.00903

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00398

Hom.:

Bravo

AF:

0.0311

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0899

AC:

396

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00855

AC:

1038

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

DANN

Benign

0.88

DEOGEN2

Benign

0.017

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.32

N;N

REVEL

Benign

0.015

Sift

Benign

0.17

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.0030

B;.

Vest4

0.13

MVP

0.50

ClinPred

0.00032

GERP RS

-1.2

gMVP

0.017

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