chr12-101733936-T-G

Position:

• chr12-101733936-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001177949.2(SYCP3):​c.354-262A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,108 control chromosomes in the GnomAD database, including 5,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5345 hom., cov: 32)
• Consequence: SYCP3 NM_001177949.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-101733936-T-G is Benign according to our data. Variant chr12-101733936-T-G is described in ClinVar as [Benign]. Clinvar id is 1259063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYCP3	NM_001177949.2	c.354-262A>C		intron_variant		ENST00000392924.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCP3	ENST00000392924.2	c.354-262A>C		intron_variant		1	NM_001177949.2	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38821 AN: 151990 Hom.: 5347 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38829 AN: 152108 Hom.: 5345 Cov.: 32 AF XY: 0.257 AC XY: 19095 AN XY: 74348

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.333

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.261

Alfa AF: 0.262 Hom.: 670

Bravo AF: 0.245

Asia WGS AF: 0.271 AC: 933 AN: 3446

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.84

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

LitVar

Other links and lift over

dbSNP: rs10860780; hg19: chr12-102127714;