Variant 1-114860747-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003176.4(SYCP1):c.536C>T(p.Thr179Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,594,154 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 7 hom. )

Consequence

SYCP1
NM_003176.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.56

Variant links:

Genes affected

SYCP1 (HGNC:11487): (synaptonemal complex protein 1) Enables double-stranded DNA binding activity. Involved in protein homotetramerization. Predicted to be located in synaptonemal complex. Predicted to be active in central element; male germ cell nucleus; and transverse filament. [provided by Alliance of Genome Resources, Apr 2022]

SYCP1 links:

SYCP1 (HGNC:):

SYCP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0132445395).

BP6

Variant 1-114860747-C-T is Benign according to our data. Variant chr1-114860747-C-T is described in ClinVar as [Benign]. Clinvar id is 746336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP1	NM_003176.4 linkuse as main transcript	c.536C>T	p.Thr179Ile	missense_variant	8/32	ENST00000369522.8	NP_003167.2	Q15431A0A024R0I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYCP1	ENST00000369522.8 linkuse as main transcript	c.536C>T	p.Thr179Ile	missense_variant	8/32	1	NM_003176.4	ENSP00000358535.3		Q15431

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0000945

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00172

AC:

404

AN:

235136

Hom.:

AF XY:

0.00210

AC XY:

268

AN XY:

127644

show subpopulations

Gnomad AFR exome

AF:

0.0000643

Gnomad AMR exome

AF:

0.000340

Gnomad ASJ exome

AF:

0.00345

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00589

Gnomad FIN exome

AF:

0.0000936

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.00193

GnomAD4 exome

AF:

0.00148

AC:

2134

AN:

1441948

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1217

AN XY:

717000

show subpopulations

Gnomad4 AFR exome

AF:

0.000154

Gnomad4 AMR exome

AF:

0.000445

Gnomad4 ASJ exome

AF:

0.00327

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00589

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00202

GnomAD4 genome

AF:

0.00101

AC:

154

AN:

152206

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.000971

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00180

AC:

218

Asia WGS

AF:

0.00116

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;T;T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

.;T;D;D;.

M_CAP

Benign

0.014

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;.;M;.;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.4

N;D;.;.;N

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D;.;.;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

1.0

D;.;D;.;D

Vest4

0.64

MVP

0.28

MPC

0.60

ClinPred

0.049

GERP RS

4.0

Varity_R

0.59

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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