10-133554319-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.229

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
SYCE1	NM_001143763.2	c.928C>G	p.Pro310Ala	missense_variant	13/13
SYCE1	NM_130784.4	c.820C>G	p.Pro274Ala	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCE1	ENST00000303903.10	c.928C>G	p.Pro310Ala	missense_variant	13/13	1		P2
CYP2E1	ENST00000368520.1	n.1359-342G>C		intron_variant, non_coding_transcript_variant		1
SYCE1	ENST00000368517.7	c.820C>G	p.Pro274Ala	missense_variant	13/13	5		A2
SYCE1	ENST00000479535.2	n.2061C>G		non_coding_transcript_exon_variant	11/11	5

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3975 AN: 151998 Hom.: 163 Cov.: 33

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.: 74 AF XY: 0.00500 AC XY: 680 AN XY: 135888

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.: 30 AF XY: 0.00222 AC XY: 1611 AN XY: 727136

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.: 33 AF XY: 0.0253 AC XY: 1883 AN XY: 74360

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.: 18

Bravo AF: 0.0311

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0899 AC: 396

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00855 AC: 1038

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	4.5
Dann	Benign	0.88
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.36	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
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	T
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

Other links and lift over

dbSNP: rs11101822; hg19: chr10-135367823;