rs8181357

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001143764.3(SYCE1):c.396G>T(p.Glu132Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,611,392 control chromosomes in the GnomAD database, including 11,017 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.098 ( 882 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10135 hom. )

Consequence

SYCE1
NM_001143764.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.669

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002853632).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYCE1	NM_001143764.3 link	c.396G>T	p.Glu132Asp	missense_variant	Exon 7 of 13	ENST00000343131.7	NP_001137236.1
SYCE1	NM_001143763.2 link	c.396G>T	p.Glu132Asp	missense_variant	Exon 7 of 13		NP_001137235.1	Q8N0S2A0A0B4J1R9
SYCE1	NM_130784.4 link	c.288G>T	p.Glu96Asp	missense_variant	Exon 7 of 13		NP_570140.1	Q8N0S2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000343131.7 link	c.396G>T	p.Glu132Asp	missense_variant	Exon 7 of 13	1	NM_001143764.3	ENSP00000341282.5		Q8N0S2-1

Frequencies

GnomAD3 genomes

AF:

0.0978

AC:

14860

AN:

152014

Hom.:

879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.0995

GnomAD2 exomes

AF:

0.126

AC:

31638

AN:

251084

AF XY:

0.127

show subpopulations

Gnomad AFR exome

AF:

0.0566

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.0970

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.124

Gnomad NFE exome

AF:

0.0932

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.109

AC:

159706

AN:

1459260

Hom.:

10135

Cov.:

AF XY:

0.111

AC XY:

80583

AN XY:

726018

show subpopulations

Gnomad4 AFR exome

AF:

0.0556

AC:

1856

AN:

33390

Gnomad4 AMR exome

AF:

0.153

AC:

6854

AN:

44660

Gnomad4 ASJ exome

AF:

0.0993

AC:

2592

AN:

26100

Gnomad4 EAS exome

AF:

0.267

AC:

10584

AN:

39662

Gnomad4 SAS exome

AF:

0.188

AC:

16149

AN:

86074

Gnomad4 FIN exome

AF:

0.121

AC:

6458

AN:

53342

Gnomad4 NFE exome

AF:

0.0973

AC:

107976

AN:

1109990

Gnomad4 Remaining exome

AF:

0.112

AC:

6759

AN:

60280

Heterozygous variant carriers

7633

15266

22900

30533

38166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

4204

8408

12612

16816

21020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0977

AC:

14867

AN:

152132

Hom.:

882

Cov.:

AF XY:

0.103

AC XY:

7636

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0576

AC:

0.0576422

AN:

0.0576422

Gnomad4 AMR

AF:

0.125

AC:

0.124738

AN:

0.124738

Gnomad4 ASJ

AF:

0.101

AC:

0.101094

AN:

0.101094

Gnomad4 EAS

AF:

0.253

AC:

0.252914

AN:

0.252914

Gnomad4 SAS

AF:

0.193

AC:

0.193488

AN:

0.193488

Gnomad4 FIN

AF:

0.120

AC:

0.120377

AN:

0.120377

Gnomad4 NFE

AF:

0.0942

AC:

0.0941976

AN:

0.0941976

Gnomad4 OTH

AF:

0.0980

AC:

0.0980114

AN:

0.0980114

Heterozygous variant carriers

659

1318

1977

2636

3295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0987

Hom.:

2378

Bravo

AF:

0.0960

TwinsUK

AF:

0.109

AC:

404

ALSPAC

AF:

0.0963

AC:

371

ESP6500AA

AF:

0.0622

AC:

274

ESP6500EA

AF:

0.0956

AC:

822

ExAC

AF:

0.123

AC:

14899

EpiCase

AF:

0.0956

EpiControl

AF:

0.0935

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T;T

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.55

T;T;T

MetaRNN

Benign

0.0029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.061

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.080

T;T;T

Polyphen

0.015

B;.;B

Vest4

0.12

MutPred

0.072

.;Loss of ubiquitination at K134 (P = 0.1191);Loss of ubiquitination at K134 (P = 0.1191);

MPC

0.18

ClinPred

0.0071

GERP RS

0.22

Varity_R

0.11

gMVP

0.028

Mutation Taster

=99/1

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over