Genetic Variant NM_001139456.2:c.985G>C (chr7-138628242-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001139456.2(SVOPL):c.985G>C(p.Glu329Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,876 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. 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. E329K) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SVOPL
NM_001139456.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.14

Publications

0 publications found

Variant links:

Genes affected

SVOPL (HGNC:27034): (SVOP like) The protein encoded by this gene is thought to be a member of solute carrier family 22, which includes transmembrane proteins that transport toxins and drugs from the body. This gene is a paralog of the SVOP gene that encodes synaptic vesicle 2-related protein. [provided by RefSeq, Sep 2016]

SVOPL links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39747497).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001139456.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SVOPL	NM_001139456.2	MANE Select	c.985G>C	p.Glu329Gln	missense	Exon 11 of 16	NP_001132928.1	Q8N434-1
SVOPL	NM_001331192.1		c.712G>C	p.Glu238Gln	missense	Exon 8 of 13	NP_001318121.1
SVOPL	NM_174959.3		c.529G>C	p.Glu177Gln	missense	Exon 7 of 12	NP_777619.1	Q8N434-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SVOPL	ENST00000674285.1	MANE Select	c.985G>C	p.Glu329Gln	missense	Exon 11 of 16	ENSP00000501457.1	Q8N434-1
SVOPL	ENST00000436657.5	TSL:1	c.529G>C	p.Glu177Gln	missense	Exon 7 of 12	ENSP00000417018.1	Q8N434-2
SVOPL	ENST00000419765.4	TSL:5	c.985G>C	p.Glu329Gln	missense	Exon 10 of 15	ENSP00000405482.2	Q8N434-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.011

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.8

PhyloP100

5.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.69

REVEL

Benign

0.11

Sift

Benign

0.18

Sift4G

Benign

0.34

Polyphen

0.0070

Vest4

0.59

MutPred

0.43

Loss of phosphorylation at S327 (P = 0.1641)

MVP

0.30

MPC

0.032

ClinPred

0.44

GERP RS

4.6

Varity_R

0.15

gMVP

0.84

Mutation Taster

=88/12

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over