7-138621122-G-T

Position:

• chr7-138621122-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001139456.2(SVOPL):​c.1277C>A​(p.Thr426Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SVOPL NM_001139456.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27401948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVOPL	NM_001139456.2	c.1277C>A	p.Thr426Lys	missense_variant	14/16	ENST00000674285.1	NP_001132928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVOPL	ENST00000674285.1	c.1277C>A	p.Thr426Lys	missense_variant	14/16		NM_001139456.2	ENSP00000501457.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461392 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726990

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

The c.1277C>A (p.T426K) alteration is located in exon 13 (coding exon 13) of the SVOPL gene. This alteration results from a C to A substitution at nucleotide position 1277, causing the threonine (T) at amino acid position 426 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.054	.;.;.;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.79	T;T;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.86	.;.;.;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.0	N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.079	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.082	B;.;B;B
Vest4		0.60
MutPred		0.53		.;.;.;Gain of ubiquitination at T426 (P = 0.0289);
MVP		0.55
MPC		0.074
ClinPred		0.13	T
GERP RS		4.4
Varity_R		0.11
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-138305867;