Variant 1-114857466-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003176.4(SYCP1):c.260A>G(p.Tyr87Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,600,976 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0048 ( 28 hom. )

Consequence

SYCP1
NM_003176.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.56

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010768622).

BP6

Variant 1-114857466-A-G is Benign according to our data. Variant chr1-114857466-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 787754.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 28 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYCP1	NM_003176.4 linkuse as main transcript	c.260A>G	p.Tyr87Cys	missense_variant	5/32	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.260A>G	p.Tyr87Cys	missense_variant	5/32	1	NM_003176.4	ENSP00000358535.3		Q15431

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

413

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00290

AC:

708

AN:

244002

Hom.:

AF XY:

0.00316

AC XY:

416

AN XY:

131780

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.00184

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00400

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00433

Gnomad OTH exome

AF:

0.00304

GnomAD4 exome

AF:

0.00479

AC:

6934

AN:

1448734

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

3373

AN XY:

720178

show subpopulations

Gnomad4 AFR exome

AF:

0.000635

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00471

Gnomad4 FIN exome

AF:

0.000962

Gnomad4 NFE exome

AF:

0.00557

Gnomad4 OTH exome

AF:

0.00378

GnomAD4 genome

AF:

0.00271

AC:

413

AN:

152242

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

197

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00452

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00430

Hom.:

Bravo

AF:

0.00290

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00560

AC:

ExAC

AF:

0.00287

AC:

348

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Mycotic Aneurysm, Intracranial

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Brain Center Rudolf Magnus, University Medical Center Utrecht

Oct 08, 2021

- -

not provided

Benign:1

Likely 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

Benign

0.086

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;T;T;T

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

.;T;T;T;.

M_CAP

Benign

0.0083

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;.;M

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.4

N;N;.;.;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.011

D;D;.;.;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.99

D;.;D;.;D

Vest4

0.52

MVP

0.21

MPC

0.76

ClinPred

0.024

GERP RS

1.7

Varity_R

0.15

gMVP

0.074

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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