chr1-42816436-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_199342.4(SVBP):c.109G>A(p.Ala37Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SVBP
NM_199342.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.08

Publications

0 publications found

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:

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

TMEM269 links:

Genome browser will be placed here

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;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.3744 (below the threshold of 3.09). Trascript score misZ: 0.51921 (below the threshold of 3.09). GenCC associations: The gene is linked to syndromic intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.2176533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVBP	NM_199342.4 link	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 3	ENST00000372521.9	NP_955374.1	Q8N300
SVBP	XM_017001226.2 link	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 3		XP_016856715.1	Q8N300

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SVBP	ENST00000372521.9 link	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 3	1	NM_199342.4	ENSP00000361599.4	Q8N300
SVBP	ENST00000372522.5 link	c.109G>A	p.Ala37Thr	missense_variant	Exon 2 of 3	3		ENSP00000361600.1	Q8N300
SVBP	ENST00000497437.1 link	n.208G>A		non_coding_transcript_exon_variant	Exon 2 of 3	3
TMEM269	ENST00000421630.6 link	n.*424-99C>T		intron_variant	Intron 10 of 10	5		ENSP00000490287.1	A0A1B0GVZ9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

May 03, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.109G>A (p.A37T) alteration is located in exon 2 (coding exon 1) of the SVBP gene. This alteration results from a G to A substitution at nucleotide position 109, causing the alanine (A) at amino acid position 37 to be replaced by a threonine (T). 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

0.61

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.017

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.0097

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.90

PhyloP100

5.1

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.7

D;D

REVEL

Benign

0.15

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.066

T;T

Polyphen

0.0020

B;B

Vest4

0.62

MutPred

0.20

Gain of loop (P = 0.0121);Gain of loop (P = 0.0121);

MVP

0.15

MPC

1.1

ClinPred

0.99

GERP RS

4.3

PromoterAI

0.0081

Neutral

(source)

Varity_R

0.77

gMVP

0.097

Mutation Taster

=44/56

disease causing

(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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chr1-42816436-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over