dbSNP rs2987800: SYCE1:p.Gln9Leu (chr10-133568423-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000432597.3(SYCE1):c.26A>T(p.Gln9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000475 in 631,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q9Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

SYCE1
ENST00000432597.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.98

Publications

9 publications found

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:

SPRNP1 (HGNC:37819): (shadow of prion protein pseudogene 1)

SPRNP1 links:

ENSG00000288107 (HGNC:):

ENSG00000288107 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12142724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPRNP1	NR_033789.2 link	n.752A>T		non_coding_transcript_exon_variant	Exon 2 of 2
SYCE1	NM_130784.4 link	c.-271A>T		upstream_gene_variant			NP_570140.1	Q8N0S2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
SYCE1	ENST00000432597.3 link	c.26A>T	p.Gln9Leu	missense_variant	Exon 2 of 2	1	ENSP00000411779.3	A0A0A0MT28
ENSG00000288107	ENST00000655152.1 link	n.445+2120T>A		intron_variant	Intron 1 of 1
ENSG00000288107	ENST00000656338.1 link	n.507+2120T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

479534

Hom.:

Cov.:

AF XY:

0.00000385

AC XY:

AN XY:

259866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11448

American (AMR)

AF:

0.00

AC:

AN:

24920

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14688

East Asian (EAS)

AF:

0.00

AC:

AN:

27744

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53178

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2070

European-Non Finnish (NFE)

AF:

0.00000361

AC:

AN:

277134

Other (OTH)

AF:

0.00

AC:

AN:

25634

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41282

American (AMR)

AF:

0.00

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67970

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

9563

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.4

(source)

DANN

Benign

0.45

FATHMM_MKL

Benign

0.00056

LIST_S2

Benign

0.16

MetaRNN

Benign

0.12

PhyloP100

-3.0

Sift4G

Benign

0.15

Vest4

0.096

MVP

0.61

GERP RS

-0.59

PromoterAI

-0.0057

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over