Genetic Variant SYCE3:p.Arg60His (chr22-50551333-C-T) – 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 NM_001123225.3(SYCE3):c.179G>A(p.Arg60His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,551,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SYCE3
NM_001123225.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Publications

0 publications found

Variant links:

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]

SYCE3 links:

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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=0.16353256).

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.179G>A	p.Arg60His	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.179G>A	p.Arg60His	missense	Exon 3 of 3	ENSP00000385480.3	A1L190
	SYCE3	ENST00000402753.1	TSL:1	c.179G>A	p.Arg60His	missense	Exon 2 of 2	ENSP00000385122.1	A1L190

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152170

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000325

AC:

AN:

154052

AF XY:

0.0000367

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1399016

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

690024

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31598

American (AMR)

AF:

0.0000840

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000379

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48906

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000741

AC:

AN:

1078950

Other (OTH)

AF:

0.00

AC:

AN:

58006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.432

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000383

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.43

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.77

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.98

PhyloP100

1.7

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.13

Sift

Benign

0.056

Sift4G

Uncertain

0.031

Polyphen

0.67

Vest4

0.13

MutPred

0.32

Loss of MoRF binding (P = 0.0635)

MVP

0.21

ClinPred

0.19

GERP RS

5.0

Varity_R

0.13

gMVP

0.63

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over