chr7-138621092-C-A

Variant names:

• chr7-138621092-C-A
• NM_001139456.2:c.1307G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001139456.2(SVOPL):​c.1307G>T​(p.Gly436Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SVOPL NM_001139456.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVOPL	NM_001139456.2	MANE Select	c.1307G>T	p.Gly436Val	missense	Exon 14 of 16	NP_001132928.1	Q8N434-1
	SVOPL	NM_001331192.1		c.1034G>T	p.Gly345Val	missense	Exon 11 of 13	NP_001318121.1
	SVOPL	NM_174959.3		c.851G>T	p.Gly284Val	missense	Exon 10 of 12	NP_777619.1	Q8N434-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVOPL	ENST00000674285.1	MANE Select	c.1307G>T	p.Gly436Val	missense	Exon 14 of 16	ENSP00000501457.1	Q8N434-1
	SVOPL	ENST00000436657.5	TSL:1	c.851G>T	p.Gly284Val	missense	Exon 10 of 12	ENSP00000417018.1	Q8N434-2
	SVOPL	ENST00000419765.4	TSL:5	c.1307G>T	p.Gly436Val	missense	Exon 13 of 15	ENSP00000405482.2	Q8N434-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.67
Sift	Benign	0.037	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.75		Loss of disorder (P = 0.0494)
MVP		0.86
MPC		0.17
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.72
gMVP		0.65
Mutation Taster		=66/34	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

hg19: chr7-138305837;