NM_001123225.3:c.199G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001123225.3(SYCE3):​c.199G>A​(p.Val67Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00612 in 1,551,270 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (46 hom.)
• Consequence: SYCE3 NM_001123225.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00575307).
• BP6: Variant 22-50551313-C-T is Benign according to our data. Variant chr22-50551313-C-T is described in ClinVar as Benign. ClinVar VariationId is 2653406.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 46 AR gene

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>A	p.Val67Ile	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>A	p.Val67Ile	missense	Exon 3 of 3	ENSP00000385480.3	A1L190
	SYCE3	ENST00000402753.1	TSL:1	c.199G>A	p.Val67Ile	missense	Exon 2 of 2	ENSP00000385122.1	A1L190

Frequencies

GnomAD3 genomes AF: 0.00467 AC: 710 AN: 152152 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00689

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00467 AC: 719 AN: 154020 AF XY: 0.00454

Gnomad AFR exome AF: 0.000757

Gnomad AMR exome AF: 0.00109

Gnomad ASJ exome AF: 0.00565

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0121

Gnomad NFE exome AF: 0.00691

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00628 AC: 8784 AN: 1399000 Hom.: 46 Cov.: 31 AF XY: 0.00611 AC XY: 4214 AN XY: 690022

African (AFR) AF: 0.00101 AC: 32 AN: 31598

American (AMR) AF: 0.00118 AC: 42 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 160 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.000833 AC: 66 AN: 79236

European-Finnish (FIN) AF: 0.0123 AC: 604 AN: 48908

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5698

European-Non Finnish (NFE) AF: 0.00701 AC: 7559 AN: 1078936

Other (OTH) AF: 0.00547 AC: 317 AN: 58002

GnomAD4 genome AF: 0.00466 AC: 709 AN: 152270 Hom.: 1 Cov.: 33 AF XY: 0.00469 AC XY: 349 AN XY: 74454

African (AFR) AF: 0.00120 AC: 50 AN: 41546

American (AMR) AF: 0.00137 AC: 21 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00689 AC: 469 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00585 Hom.: 6

Bravo AF: 0.00352

TwinsUK AF: 0.00485 AC: 18

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00289 AC: 4

ESP6500EA AF: 0.00660 AC: 21

ExAC AF: 0.00357 AC: 94

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.5
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.56	N
REVEL	Benign	0.014
Sift	Benign	0.10	T
Sift4G	Benign	0.26	T
Polyphen		0.079	B
Vest4		0.15
MVP		0.081
ClinPred		0.0074	T
GERP RS		2.4
Varity_R		0.033
gMVP		0.43
Mutation Taster		=99/1	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;