chr10-133555402-G-C

Position:

• chr10-133555402-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001143764.3(SYCE1):​c.867C>G​(p.Val289Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,614,108 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (40 hom.)
• Consequence: SYCE1 NM_001143764.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.249

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-133555402-G-C is Benign according to our data. Variant chr10-133555402-G-C is described in ClinVar as [Benign]. Clinvar id is 711322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-133555402-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.249 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCE1	NM_001143764.3	c.867C>G	p.Val289Val	synonymous_variant	12/13	ENST00000343131.7	NP_001137236.1
SYCE1	NM_001143763.2	c.867C>G	p.Val289Val	synonymous_variant	12/13		NP_001137235.1
SYCE1	NM_130784.4	c.759C>G	p.Val253Val	synonymous_variant	12/13		NP_570140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000343131.7	c.867C>G	p.Val289Val	synonymous_variant	12/13	1	NM_001143764.3	ENSP00000341282.5

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 543 AN: 152194 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00564

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00402 AC: 1011 AN: 251452 Hom.: 10 AF XY: 0.00442 AC XY: 601 AN XY: 135896

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.00506

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00549

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.00527

Gnomad OTH exome AF: 0.00635

GnomAD4 exome AF: 0.00488 AC: 7133 AN: 1461796 Hom.: 40 Cov.: 33 AF XY: 0.00497 AC XY: 3617 AN XY: 727202

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00250

Gnomad4 ASJ exome AF: 0.00574

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00616

Gnomad4 FIN exome AF: 0.00262

Gnomad4 NFE exome AF: 0.00518

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.00357 AC: 543 AN: 152312 Hom.: 4 Cov.: 33 AF XY: 0.00357 AC XY: 266 AN XY: 74466

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00871

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00564

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00398 Hom.: 2

Bravo AF: 0.00346

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.60

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: rs138177213; hg19: chr10-135368906;