12-101729122-AT-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BS2_Supporting

The NM_001177949.2(SYCP3):​c.643del​(p.Ile215LeufsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000696 in 1,594,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SYCP3
NM_001177949.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.782
Variant links:
Genes affected
SYCP3 (HGNC:18130): (synaptonemal complex protein 3) This gene encodes an essential structural component of the synaptonemal complex. This complex is involved in synapsis, recombination and segregation of meiotic chromosomes. Mutations in this gene are associated with azoospermia in males and susceptibility to pregnancy loss in females. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, May 2010]
CHPT1 (HGNC:17852): (choline phosphotransferase 1) Enables diacylglycerol cholinephosphotransferase activity. Involved in phosphatidylcholine biosynthetic process and platelet activating factor biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5
Variant 12-101729122-AT-A is Pathogenic according to our data. Variant chr12-101729122-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 5371.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SYCP3NM_001177949.2 linkuse as main transcriptc.643del p.Ile215LeufsTer2 frameshift_variant 8/9 ENST00000392924.2
CHPT1NM_020244.3 linkuse as main transcript downstream_gene_variant ENST00000229266.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SYCP3ENST00000392924.2 linkuse as main transcriptc.643del p.Ile215LeufsTer2 frameshift_variant 8/91 NM_001177949.2 P1
CHPT1ENST00000229266.8 linkuse as main transcript downstream_gene_variant 1 NM_020244.3 P1Q8WUD6-1

Frequencies

GnomAD3 genomes
AF:
0.0000397
AC:
6
AN:
151136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000132
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000443
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000727
AC:
105
AN:
1443358
Hom.:
0
Cov.:
30
AF XY:
0.0000793
AC XY:
57
AN XY:
718392
show subpopulations
Gnomad4 AFR exome
AF:
0.000121
Gnomad4 AMR exome
AF:
0.0000910
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.000200
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000692
Gnomad4 OTH exome
AF:
0.0000503
GnomAD4 genome
AF:
0.0000397
AC:
6
AN:
151136
Hom.:
0
Cov.:
32
AF XY:
0.0000407
AC XY:
3
AN XY:
73750
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000132
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000443
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000421
Hom.:
0

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spermatogenic failure 4 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 22, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

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.

Other links and lift over

dbSNP: rs761136347; hg19: chr12-102122900; API