12-101731674-TATAAA-T

Position:

• chr12-101731674-TATAAA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001177949.2(SYCP3):​c.454-13_454-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 1,574,740 control chromosomes in the GnomAD database, including 3,282 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (328 hom., cov: 32)
  • Exomes 𝑓: 0.021 (2954 hom.)
• Consequence: SYCP3 NM_001177949.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.48

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 -16 ACMG points.

• BP6: Variant 12-101731674-TATAAA-T is Benign according to our data. Variant chr12-101731674-TATAAA-T is described in ClinVar as [Benign]. Clinvar id is 306763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYCP3	NM_001177949.2	c.454-13_454-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392924.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCP3	ENST00000392924.2	c.454-13_454-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001177949.2	P1

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3318 AN: 152020 Hom.: 328 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0205

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.0244

GnomAD3 exomes AF: 0.0445 AC: 9705 AN: 217934 Hom.: 1076 AF XY: 0.0468 AC XY: 5551 AN XY: 118512

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.0293

Gnomad EAS exome AF: 0.321

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.00446

Gnomad OTH exome AF: 0.0272

GnomAD4 exome AF: 0.0211 AC: 30064 AN: 1422602 Hom.: 2954 AF XY: 0.0239 AC XY: 16907 AN XY: 707214

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.00442

Gnomad4 ASJ exome AF: 0.0303

Gnomad4 EAS exome AF: 0.324

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0186

Gnomad4 NFE exome AF: 0.00339

Gnomad4 OTH exome AF: 0.0332

GnomAD4 genome AF: 0.0218 AC: 3321 AN: 152138 Hom.: 328 Cov.: 32 AF XY: 0.0264 AC XY: 1961 AN XY: 74396

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0205

Gnomad4 NFE AF: 0.00466

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0123 Hom.: 12

Bravo AF: 0.0191

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spermatogenic Failure Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs145003954; hg19: chr12-102125452;