Variant 10-133568423-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000432597.3(SYCE1):c.26A>C(p.Gln9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 630,732 control chromosomes in the GnomAD database, including 225,290 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 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 0.73 ( 43906 hom., cov: 32)

Exomes 𝑓: 0.87 ( 181384 hom. )

Consequence

SYCE1
ENST00000432597.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.98

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:):

SPRNP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00138551).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPRNP1	NR_033789.2 linkuse as main transcript	n.752A>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
SYCE1	ENST00000432597.3 linkuse as main transcript	c.26A>C	p.Gln9Pro	missense_variant	2/2	1	ENSP00000411779.3	A0A0A0MT28
ENSG00000288107	ENST00000655152.1 linkuse as main transcript	n.445+2120T>G		intron_variant
ENSG00000288107	ENST00000656338.1 linkuse as main transcript	n.507+2120T>G		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110283

AN:

151672

Hom.:

43887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.936

Gnomad AMR

AF:

0.793

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.846

Gnomad FIN

AF:

0.921

Gnomad MID

AF:

0.780

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.750

GnomAD4 exome

AF:

0.868

AC:

415589

AN:

478942

Hom.:

181384

Cov.:

AF XY:

0.870

AC XY:

225781

AN XY:

259578

show subpopulations

Gnomad4 AFR exome

AF:

0.367

Gnomad4 AMR exome

AF:

0.843

Gnomad4 ASJ exome

AF:

0.843

Gnomad4 EAS exome

AF:

0.832

Gnomad4 SAS exome

AF:

0.865

Gnomad4 FIN exome

AF:

0.915

Gnomad4 NFE exome

AF:

0.892

Gnomad4 OTH exome

AF:

0.830

GnomAD4 genome

AF:

0.727

AC:

110341

AN:

151790

Hom.:

43906

Cov.:

AF XY:

0.732

AC XY:

54321

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.793

Gnomad4 ASJ

AF:

0.832

Gnomad4 EAS

AF:

0.822

Gnomad4 SAS

AF:

0.846

Gnomad4 FIN

AF:

0.921

Gnomad4 NFE

AF:

0.890

Gnomad4 OTH

AF:

0.753

Alfa

AF:

0.796

Hom.:

8584

TwinsUK

AF:

0.905

AC:

3354

ALSPAC

AF:

0.894

AC:

3444

Asia WGS

AF:

0.807

AC:

2805

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.97

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.4

DANN

Benign

0.41

FATHMM_MKL

Benign

0.000040

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0014

Sift4G

Benign

0.44

Vest4

0.12

MVP

0.61

GERP RS

-0.59

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over