22-50551313-C-G

Variant names:

• chr22-50551313-C-G
• rs55829948
• NM_001123225.3:c.199G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001123225.3(SYCE3):​c.199G>C​(p.Val67Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. V67I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SYCE3 NM_001123225.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 9 publications found

Genes affected

SYCE3 (HGNC:35245): (synaptonemal complex central element protein 3) Predicted to be involved in reciprocal meiotic recombination; spermatogenesis; and synaptonemal complex assembly. Predicted to act upstream of or within positive regulation of apoptotic process. Predicted to be located in chromosome and nucleus. Predicted to be active in central element. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041432828).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123225.3. 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
	SYCE3	NM_001123225.3	MANE Select	c.199G>C	p.Val67Leu	missense	Exon 3 of 3	NP_001116697.1	A1L190

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCE3	ENST00000406915.4	TSL:2 MANE Select	c.199G>C	p.Val67Leu	missense	Exon 3 of 3	ENSP00000385480.3	A1L190
	SYCE3	ENST00000402753.1	TSL:1	c.199G>C	p.Val67Leu	missense	Exon 2 of 2	ENSP00000385122.1	A1L190

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.066	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.99	T
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.045
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.074
MutPred		0.17		Loss of ubiquitination at K70 (P = 0.1172)
MVP		0.081
ClinPred		0.055	T
GERP RS		2.4
Varity_R		0.044
gMVP		0.51
Mutation Taster		=95/5	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: rs55829948; hg19: chr22-50989742;