rs889352214

Variant names:

• chr10-133555877-C-A
• rs889352214
• NM_001143764.3:c.622G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-133555877-C-A
• chr10-133555877-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001143764.3(SYCE1):​c.622G>T​(p.Asp208Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D208N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SYCE1 NM_001143764.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143764.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCE1	NM_001143764.3	MANE Select	c.622G>T	p.Asp208Tyr	missense	Exon 10 of 13	NP_001137236.1	Q8N0S2-1
	SYCE1	NM_001143763.2		c.622G>T	p.Asp208Tyr	missense	Exon 10 of 13	NP_001137235.1	A0A0B4J1R9
	SYCE1	NM_130784.4		c.514G>T	p.Asp172Tyr	missense	Exon 10 of 13	NP_570140.1	Q8N0S2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCE1	ENST00000343131.7	TSL:1 MANE Select	c.622G>T	p.Asp208Tyr	missense	Exon 10 of 13	ENSP00000341282.5	Q8N0S2-1
	SYCE1	ENST00000303903.10	TSL:1	c.622G>T	p.Asp208Tyr	missense	Exon 10 of 13	ENSP00000303978.5	A0A0B4J1R9
	CYP2E1	ENST00000368520.1	TSL:1	n.2575C>A		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461734 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727152

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111946

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.8
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.56		Loss of disorder (P = 0.0095)
MVP		0.67
MPC		0.77
ClinPred		0.93	D
GERP RS		4.4
Varity_R		0.34
gMVP		0.17
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs889352214; hg19: chr10-135369381;