Variant chr12-101728722-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001177949.2(SYCP3):c.*205G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 649,690 control chromosomes in the GnomAD database, including 247 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 58 hom., cov: 33)

Exomes 𝑓: 0.021 ( 189 hom. )

Consequence

SYCP3
NM_001177949.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.867

Variant links:

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]

SYCP3 links:

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]

CHPT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-101728722-C-T is Benign according to our data. Variant chr12-101728722-C-T is described in ClinVar as [Benign]. Clinvar id is 306759.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYCP3	NM_001177949.2 linkuse as main transcript	c.*205G>A		3_prime_UTR_variant	9/9	ENST00000392924.2
CHPT1	NM_020244.3 linkuse as main transcript	c.1177-179C>T		intron_variant		ENST00000229266.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYCP3	ENST00000392924.2 linkuse as main transcript	c.*205G>A		3_prime_UTR_variant	9/9	1	NM_001177949.2	P1
CHPT1	ENST00000229266.8 linkuse as main transcript	c.1177-179C>T		intron_variant		1	NM_020244.3	P1	Q8WUD6-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

3004

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00507

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0694

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.00953

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.0219

Gnomad OTH

AF:

0.0249

GnomAD4 exome

AF:

0.0213

AC:

10580

AN:

497470

Hom.:

189

Cov.:

AF XY:

0.0203

AC XY:

5307

AN XY:

260906

show subpopulations

Gnomad4 AFR exome

AF:

0.00417

Gnomad4 AMR exome

AF:

0.0885

Gnomad4 ASJ exome

AF:

0.00951

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00977

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.0233

Gnomad4 OTH exome

AF:

0.0230

GnomAD4 genome

AF:

0.0198

AC:

3008

AN:

152220

Hom.:

Cov.:

AF XY:

0.0191

AC XY:

1423

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.00505

Gnomad4 AMR

AF:

0.0697

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.00953

Gnomad4 NFE

AF:

0.0219

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0217

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.00811

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spermatogenic failure 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.1

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over