10-133568423-T-G

Variant names:

• chr10-133568423-T-G
• rs2987800
• ENST00000432597.3:c.26A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 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 0.73 (43906 hom., cov: 32)
  • Exomes 𝑓: 0.87 (181384 hom.)
• Consequence: SYCE1 ENST00000432597.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 9 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]

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

ENSG00000288107 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPRNP1	NR_033789.2	n.752A>C		non_coding_transcript_exon_variant	Exon 2 of 2
SYCE1	NM_130784.4	c.-271A>C		upstream_gene_variant			NP_570140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYCE1	ENST00000432597.3	c.26A>C	p.Gln9Pro	missense_variant	Exon 2 of 2	1		ENSP00000411779.3
ENSG00000288107	ENST00000655152.1	n.445+2120T>G		intron_variant	Intron 1 of 1
ENSG00000288107	ENST00000656338.1	n.507+2120T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110283 AN: 151672 Hom.: 43887 Cov.: 32

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.: 4 AF XY: 0.870 AC XY: 225781 AN XY: 259578

African (AFR) AF: 0.367 AC: 4168 AN: 11342

American (AMR) AF: 0.843 AC: 20997 AN: 24896

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 12363 AN: 14668

East Asian (EAS) AF: 0.832 AC: 23040 AN: 27680

South Asian (SAS) AF: 0.865 AC: 45961 AN: 53162

European-Finnish (FIN) AF: 0.915 AC: 39071 AN: 42684

Middle Eastern (MID) AF: 0.811 AC: 1674 AN: 2064

European-Non Finnish (NFE) AF: 0.892 AC: 247072 AN: 276866

Other (OTH) AF: 0.830 AC: 21243 AN: 25580

GnomAD4 genome AF: 0.727 AC: 110341 AN: 151790 Hom.: 43906 Cov.: 32 AF XY: 0.732 AC XY: 54321 AN XY: 74222

African (AFR) AF: 0.342 AC: 14127 AN: 41258

American (AMR) AF: 0.793 AC: 12125 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2886 AN: 3470

East Asian (EAS) AF: 0.822 AC: 4187 AN: 5092

South Asian (SAS) AF: 0.846 AC: 4078 AN: 4818

European-Finnish (FIN) AF: 0.921 AC: 9761 AN: 10602

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.890 AC: 60512 AN: 67954

Other (OTH) AF: 0.753 AC: 1586 AN: 2106

Alfa AF: 0.773 Hom.: 9563

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
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.97	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.41
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0014	T
PhyloP100		-3.0
Sift4G	Benign	0.44	T
Vest4		0.12
MVP		0.61
GERP RS		-0.59
PromoterAI		0.0035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2987800; hg19: chr10-135381927; COSMIC: COSV58219807; COSMIC: COSV58219807;