dbSNP rs756191256: SYVN1:p.His358Leu (chr11-65130692-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_172230.3(SYVN1):c.1073A>T(p.His358Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H358P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SYVN1
NM_172230.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023736328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYVN1	NM_172230.3 link	c.1073A>T	p.His358Leu	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>T	p.His358Leu	missense_variant	Exon 11 of 16	1	NM_172230.3	ENSP00000366395.3		Q86TM6-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

13636

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

339728

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

173046

African (AFR)

AF:

0.00

AC:

AN:

8230

American (AMR)

AF:

0.00

AC:

AN:

11096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5656

East Asian (EAS)

AF:

0.00

AC:

AN:

11000

South Asian (SAS)

AF:

0.00

AC:

AN:

30970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

986

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

245306

Other (OTH)

AF:

0.00

AC:

AN:

14800

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

13636

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

6322

African (AFR)

AF:

0.00

AC:

AN:

3764

American (AMR)

AF:

0.00

AC:

AN:

1318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

354

East Asian (EAS)

AF:

0.00

AC:

AN:

330

South Asian (SAS)

AF:

0.00

AC:

AN:

352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

946

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

6354

Other (OTH)

AF:

0.00

AC:

AN:

142

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000110

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.29

.;T;.;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.68

.;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.024

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.;L

PhyloP100

0.66

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.19

B;B;B;B

Vest4

0.24

MutPred

0.40

Gain of stability (P = 0.0386);Gain of stability (P = 0.0386);.;Gain of stability (P = 0.0386);

MVP

0.20

MPC

0.035

ClinPred

0.19

GERP RS

4.7

Varity_R

0.081

gMVP

0.16

Mutation Taster

=87/13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over