chr12-101729108-C-C

Variant names:

• chr12-101729108-C-C
• ENST00000229266.8:c.

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000229266.8(CHPT1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHPT1 ENST00000229266.8 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

Genes affected

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]

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]

SYCP3 Gene-Disease associations (from GenCC):

• infertility disorder

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• spermatogenic failure 4

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000229266.8. 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
	SYCP3	NM_001177949.2	MANE Select	c.		splice_donor intron	N/A	NP_001171420.1	Q8IZU3
	SYCP3	NM_001177948.2		c.		splice_donor intron	N/A	NP_001171419.1	Q8IZU3
	SYCP3	NM_153694.5		c.		splice_donor intron	N/A	NP_710161.1	Q8IZU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHPT1	ENST00000229266.8	TSL:1 MANE Select	c.		exon_region	Exon 9 of 9	ENSP00000229266.3	Q8WUD6-1
	SYCP3	ENST00000392924.2	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000376655.1	Q8IZU3
	SYCP3	ENST00000266743.6	TSL:1	c.		splice_donor intron	N/A	ENSP00000266743.2	Q8IZU3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-102122886;