chr12-101728682-TAGAG-T

Position:

• chr12-101728682-TAGAG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001177949.2(SYCP3):​c.*241_*244del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 519,402 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (15 hom.)
• Consequence: SYCP3 NM_001177949.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42

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 -10 ACMG points.

• BP6: Variant 12-101728682-TAGAG-T is Benign according to our data. Variant chr12-101728682-TAGAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 306758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00767 (2816/367078) while in subpopulation MID AF= 0.029 (45/1550). AF 95% confidence interval is 0.0223. There are 15 homozygotes in gnomad4_exome. There are 1457 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1005 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYCP3	NM_001177949.2	c.*241_*244del		3_prime_UTR_variant	9/9	ENST00000392924.2
CHPT1	NM_020244.3	c.1177-215_1177-212del		intron_variant		ENST00000229266.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCP3	ENST00000392924.2	c.*241_*244del		3_prime_UTR_variant	9/9	1	NM_001177949.2	P1
CHPT1	ENST00000229266.8	c.1177-215_1177-212del		intron_variant		1	NM_020244.3	P1

Frequencies

GnomAD3 genomes AF: 0.00661 AC: 1006 AN: 152206 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.00895

Gnomad OTH AF: 0.00910

GnomAD4 exome AF: 0.00767 AC: 2816 AN: 367078 Hom.: 15 AF XY: 0.00754 AC XY: 1457 AN XY: 193232

Gnomad4 AFR exome AF: 0.00205

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.0265

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00449

Gnomad4 FIN exome AF: 0.00266

Gnomad4 NFE exome AF: 0.00825

Gnomad4 OTH exome AF: 0.00989

GnomAD4 genome AF: 0.00660 AC: 1005 AN: 152324 Hom.: 5 Cov.: 32 AF XY: 0.00648 AC XY: 483 AN XY: 74480

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.0234

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00895

Gnomad4 OTH AF: 0.00900

Alfa AF: 0.00637 Hom.: 2

Bravo AF: 0.00702

Asia WGS AF: 0.00203 AC: 7 AN: 3468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spermatogenic Failure Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs370467855; hg19: chr12-102122460;