Genetic Variant SYVN1:p.Ala616Thr (chr11-65128390-C-T) – 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.1846G>A(p.Ala616Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,612,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

SYVN1
NM_172230.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.474

Publications

0 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=0.017611176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172230.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYVN1	NM_172230.3	MANE Select	c.1846G>A	p.Ala616Thr	missense	Exon 16 of 16	NP_757385.1	Q86TM6-1
	SYVN1	NM_032431.3		c.1843G>A	p.Ala615Thr	missense	Exon 16 of 16	NP_115807.1	Q86TM6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYVN1	ENST00000377190.8	TSL:1 MANE Select	c.1846G>A	p.Ala616Thr	missense	Exon 16 of 16	ENSP00000366395.3	Q86TM6-1
SYVN1	ENST00000294256.12	TSL:1	c.1843G>A	p.Ala615Thr	missense	Exon 16 of 16	ENSP00000294256.8	Q86TM6-3
SYVN1	ENST00000307289.10	TSL:1	c.1690G>A	p.Ala564Thr	missense	Exon 14 of 14	ENSP00000302035.6	Q86TM6-2

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000608

AC:

AN:

246892

AF XY:

0.0000597

show subpopulations

Gnomad AFR exome

AF:

0.000507

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000541

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000101

AC:

148

AN:

1460228

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

726396

show subpopulations

African (AFR)

AF:

0.000389

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52972

Middle Eastern (MID)

AF:

0.000187

AC:

AN:

5358

European-Non Finnish (NFE)

AF:

0.000107

AC:

119

AN:

1111610

Other (OTH)

AF:

0.000249

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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:

0.000125

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41552

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

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:

0.000225

Hom.:

Bravo

AF:

0.000204

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.80

M_CAP

Benign

0.0033

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.69

PhyloP100

0.47

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.35

REVEL

Benign

0.042

Sift

Uncertain

0.013

Sift4G

Uncertain

0.057

Polyphen

0.0

Vest4

0.069

MVP

0.10

MPC

0.030

ClinPred

0.039

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.26

Mutation Taster

=98/2

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.

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