11-65128410-T-G

Variant names:

• chr11-65128410-T-G
• rs1253181517
• NM_172230.3:c.1826A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172230.3(SYVN1):​c.1826A>C​(p.Gln609Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. Q609R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SYVN1 NM_172230.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2010701).

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.1826A>C	p.Gln609Pro	missense	Exon 16 of 16	NP_757385.1	Q86TM6-1
	SYVN1	NM_032431.3		c.1823A>C	p.Gln608Pro	missense	Exon 16 of 16	NP_115807.1	Q86TM6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYVN1	ENST00000377190.8	TSL:1 MANE Select	c.1826A>C	p.Gln609Pro	missense	Exon 16 of 16	ENSP00000366395.3	Q86TM6-1
	SYVN1	ENST00000294256.12	TSL:1	c.1823A>C	p.Gln608Pro	missense	Exon 16 of 16	ENSP00000294256.8	Q86TM6-3
	SYVN1	ENST00000307289.10	TSL:1	c.1670A>C	p.Gln557Pro	missense	Exon 14 of 14	ENSP00000302035.6	Q86TM6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.57	D
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.042	D
Polyphen		0.89	P
Vest4		0.25
MutPred		0.13		Gain of loop (P = 0.0121)
MVP		0.27
MPC		0.034
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.75
gMVP		0.45
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs1253181517; hg19: chr11-64895882;