Variant 1-42816441-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The ENST00000372521.9(SVBP):c.104A>G(p.Gln35Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SVBP
ENST00000372521.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Variant links:

Genes affected

SVBP (HGNC:29204): (small vasohibin binding protein) Enables microtubule binding activity. Involved in axon development; proteolysis; and regulation of metallopeptidase activity. Acts upstream of or within negative regulation of endothelial cell migration; negative regulation of protein ubiquitination; and protein secretion. Located in apical part of cell. [provided by Alliance of Genome Resources, Apr 2022]

SVBP links:

SVBP (HGNC:):

SVBP links:

TMEM269 (HGNC:52381): (transmembrane protein 269) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM269 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a mutagenesis_site Decreased VASH1 tyrosine carboxypeptidase activity on alpha-tubulin. (size 0) in uniprot entity SVBP_HUMAN

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVBP	NM_199342.4 linkuse as main transcript	c.104A>G	p.Gln35Arg	missense_variant	2/3	ENST00000372521.9	NP_955374.1	Q8N300
SVBP	XM_017001226.2 linkuse as main transcript	c.104A>G	p.Gln35Arg	missense_variant	2/3		XP_016856715.1	Q8N300

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SVBP	ENST00000372521.9 linkuse as main transcript	c.104A>G	p.Gln35Arg	missense_variant	2/3	1	NM_199342.4	ENSP00000361599.4	Q8N300
SVBP	ENST00000372522.5 linkuse as main transcript	c.104A>G	p.Gln35Arg	missense_variant	2/3	3		ENSP00000361600.1	Q8N300
SVBP	ENST00000497437.1 linkuse as main transcript	n.203A>G		non_coding_transcript_exon_variant	2/3	3
TMEM269	ENST00000421630.6 linkuse as main transcript	n.*424-94T>C		intron_variant		5		ENSP00000490287.1	A0A1B0GVZ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251326

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459610

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.104A>G (p.Q35R) alteration is located in exon 2 (coding exon 1) of the SVBP gene. This alteration results from a A to G substitution at nucleotide position 104, causing the glutamine (Q) at amino acid position 35 to be replaced by an arginine (R). 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

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.33

MutationTaster

Benign

0.97

D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

0.94

P;P

Vest4

0.74

MutPred

0.10

Gain of glycosylation at K32 (P = 0.0837);Gain of glycosylation at K32 (P = 0.0837);

MVP

0.30

MPC

1.1

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.87

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over