11-65130692-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_172230.3(SYVN1):c.1073A>C(p.His358Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00061 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SYVN1
NM_172230.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.656

Publications

5 publications found

Variant links:

Genes affected

SYVN1 (HGNC:20738): (synoviolin 1) This gene encodes a protein involved in endoplasmic reticulum (ER)-associated degradation. The encoded protein removes unfolded proteins, accumulated during ER stress, by retrograde transport to the cytosol from the ER. This protein also uses the ubiquitin-proteasome system for additional degradation of unfolded proteins. Sequence analysis identified two transcript variants that encode different isoforms. [provided by RefSeq, May 2011]

SYVN1 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

SYVN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004624814).

BP6

Variant 11-65130692-T-G is Benign according to our data. Variant chr11-65130692-T-G is described in ClinVar as [Benign]. Clinvar id is 403505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYVN1	NM_172230.3 link	c.1073A>C	p.His358Pro	missense_variant	Exon 11 of 16	ENST00000377190.8	NP_757385.1	Q86TM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYVN1	ENST00000377190.8 link	c.1073A>C	p.His358Pro	missense_variant	Exon 11 of 16	1	NM_172230.3	ENSP00000366395.3		Q86TM6-1

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

356

AN:

13146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.0238

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.0217

Gnomad SAS

AF:

0.0175

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0285

Gnomad OTH

AF:

0.0299

GnomAD2 exomes

AF:

0.00451

AC:

217

AN:

48092

AF XY:

0.00427

show subpopulations

Gnomad AFR exome

AF:

0.00345

Gnomad AMR exome

AF:

0.000903

Gnomad ASJ exome

AF:

0.00166

Gnomad EAS exome

AF:

0.00332

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.00619

Gnomad OTH exome

AF:

0.00194

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000610

AC:

207

AN:

339402

Hom.:

Cov.:

AF XY:

0.000596

AC XY:

103

AN XY:

172894

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000730

AC:

AN:

8218

American (AMR)

AF:

0.00126

AC:

AN:

11096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5652

East Asian (EAS)

AF:

0.00109

AC:

AN:

10988

South Asian (SAS)

AF:

0.000258

AC:

AN:

30958

European-Finnish (FIN)

AF:

0.00696

AC:

AN:

11632

Middle Eastern (MID)

AF:

0.00101

AC:

AN:

986

European-Non Finnish (NFE)

AF:

0.000339

AC:

AN:

245088

Other (OTH)

AF:

0.000135

AC:

AN:

14784

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.273

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0271

AC:

357

AN:

13174

Hom.:

Cov.:

AF XY:

0.0295

AC XY:

179

AN XY:

6078

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0279

AC:

102

AN:

3654

American (AMR)

AF:

0.0262

AC:

AN:

1298

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

346

East Asian (EAS)

AF:

0.0219

AC:

AN:

320

South Asian (SAS)

AF:

0.0202

AC:

AN:

346

European-Finnish (FIN)

AF:

0.0227

AC:

AN:

924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0285

AC:

173

AN:

6074

Other (OTH)

AF:

0.0278

AC:

AN:

144

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.274

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.212

Hom.:

ExAC

AF:

0.00106

AC:

116

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.22

.;T;.;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.48

.;T;T;T

MetaRNN

Benign

0.0046

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.58

N;N;.;N

PhyloP100

0.66

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.72

N;N;N;N

REVEL

Benign

0.093

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.0010

B;B;B;B

Vest4

0.28

MVP

0.19

MPC

0.040

ClinPred

0.0025

GERP RS

4.7

Varity_R

0.11

gMVP

0.21

Mutation Taster

=85/15

polymorphism

(source)

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.

11-65130692-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over