12-101728684-G-C

Variant names:

• chr12-101728684-G-C
• rs1952040058
• NM_001177949.2:c.*243C>G

Variant summary

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

The NM_001177949.2(SYCP3):​c.*243C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 363,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SYCP3 NM_001177949.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.43
• Publications: 0 publications found

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]

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 (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177949.2. 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.*243C>G		3_prime_UTR	Exon 9 of 9	NP_001171420.1	Q8IZU3
	CHPT1	NM_020244.3	MANE Select	c.1177-217G>C		intron	N/A	NP_064629.2	Q8WUD6-1
	SYCP3	NM_001177948.2		c.*243C>G		3_prime_UTR	Exon 9 of 9	NP_001171419.1	Q8IZU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYCP3	ENST00000392924.2	TSL:1 MANE Select	c.*243C>G		3_prime_UTR	Exon 9 of 9	ENSP00000376655.1	Q8IZU3
	SYCP3	ENST00000266743.6	TSL:1	c.*243C>G		3_prime_UTR	Exon 9 of 9	ENSP00000266743.2	Q8IZU3
	SYCP3	ENST00000392927.7	TSL:1	c.*243C>G		3_prime_UTR	Exon 9 of 9	ENSP00000376658.3	Q8IZU3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 1 AN: 363876 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 191450

African (AFR) AF: 0.00 AC: 0 AN: 10736

American (AMR) AF: 0.00 AC: 0 AN: 12314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10514

East Asian (EAS) AF: 0.0000403 AC: 1 AN: 24842

South Asian (SAS) AF: 0.00 AC: 0 AN: 31736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 229632

Other (OTH) AF: 0.00 AC: 0 AN: 20936

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Spermatogenic failure 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.84
DANN	Benign	0.59
PhyloP100		-1.4

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: rs1952040058; hg19: chr12-102122462;