10-133557853-GA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001143764.3(SYCE1):c.374+10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 1,614,076 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (28 hom.)
• Consequence: SYCE1 NM_001143764.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.506

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-133557853-GA-G is Benign according to our data. Variant chr10-133557853-GA-G is described in ClinVar as [Benign]. Clinvar id is 715410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-133557853-GA-G is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYCE1	NM_001143764.3	c.374+10del		intron_variant		ENST00000343131.7
SYCE1	NM_001143763.2	c.374+10del		intron_variant
SYCE1	NM_130784.4	c.266+10del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCE1	ENST00000343131.7	c.374+10del		intron_variant		1	NM_001143764.3	A2

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152182 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00974

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00488

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00312 AC: 784 AN: 251448 Hom.: 6 AF XY: 0.00313 AC XY: 425 AN XY: 135904

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00567

Gnomad ASJ exome AF: 0.00188

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00465

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00447 AC: 6527 AN: 1461776 Hom.: 28 Cov.: 31 AF XY: 0.00427 AC XY: 3108 AN XY: 727188

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.00590

Gnomad4 ASJ exome AF: 0.00153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000618

Gnomad4 NFE exome AF: 0.00536

Gnomad4 OTH exome AF: 0.00356

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152300 Hom.: 1 Cov.: 33 AF XY: 0.00321 AC XY: 239 AN XY: 74460

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00973

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00488

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00356 Hom.: 1

Bravo AF: 0.00392

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

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: rs571882978; hg19: chr10-135371357;