Genetic Variant SYCP3:c.*198G>A (chr12-101728729-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001177949.2(SYCP3):c.*198G>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 0.000137 in 676,784 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: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SYCP3
NM_001177949.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.544

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High AC in GnomAd4 at 20 AD gene.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYCP3	NM_001177949.2	MANE Select	c.*198G>A	3_prime_UTR	Exon 9 of 9	NP_001171420.1	Q8IZU3
CHPT1	NM_020244.3	MANE Select	c.1177-172C>T	intron	N/A	NP_064629.2	Q8WUD6-1
SYCP3	NM_001177948.2		c.*198G>A	3_prime_UTR	Exon 9 of 9	NP_001171419.1	Q8IZU3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYCP3	ENST00000392924.2	TSL:1 MANE Select	c.*198G>A	3_prime_UTR	Exon 9 of 9	ENSP00000376655.1	Q8IZU3
SYCP3	ENST00000266743.6	TSL:1	c.*198G>A	3_prime_UTR	Exon 9 of 9	ENSP00000266743.2	Q8IZU3
SYCP3	ENST00000392927.7	TSL:1	c.*198G>A	3_prime_UTR	Exon 9 of 9	ENSP00000376658.3	Q8IZU3

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000139

AC:

AN:

524498

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

274448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13684

American (AMR)

AF:

0.00

AC:

AN:

17924

Ashkenazi Jewish (ASJ)

AF:

0.0000717

AC:

AN:

13948

East Asian (EAS)

AF:

0.00

AC:

AN:

30080

South Asian (SAS)

AF:

0.00

AC:

AN:

44692

European-Finnish (FIN)

AF:

0.0000338

AC:

AN:

29566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2056

European-Non Finnish (NFE)

AF:

0.000192

AC:

AN:

344592

Other (OTH)

AF:

0.000179

AC:

AN:

27956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000131

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.000113

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Spermatogenic failure 4 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

(source)

DANN

Benign

0.56

PhyloP100

0.54

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over