rs1570520229

Variant names:

• chr1-42816502-ATTCT-A
• rs1570520229
• NM_199342.4:c.39_42delAGAA

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_199342.4(SVBP):​c.39_42delAGAA​(p.Lys13AsnfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SVBP NM_199342.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.25
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 5 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-42816502-ATTCT-A is Pathogenic according to our data. Variant chr1-42816502-ATTCT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 635969.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199342.4. 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
	SVBP	NM_199342.4	MANE Select	c.39_42delAGAA	p.Lys13AsnfsTer18	frameshift	Exon 2 of 3	NP_955374.1	Q8N300

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SVBP	ENST00000372521.9	TSL:1 MANE Select	c.39_42delAGAA	p.Lys13AsnfsTer18	frameshift	Exon 2 of 3	ENSP00000361599.4	Q8N300
	SVBP	ENST00000372522.5	TSL:3	c.39_42delAGAA	p.Lys13AsnfsTer18	frameshift	Exon 2 of 3	ENSP00000361600.1	Q8N300
	SVBP	ENST00000881555.1		c.39_42delAGAA	p.Lys13AsnfsTer18	frameshift	Exon 2 of 3	ENSP00000551614.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Lower limb spasticity;C3714756:Intellectual disability;C4551563:Microcephaly (1)
1	-	-	Neurodevelopmental disorder with ataxia, hypotonia, and microcephaly (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=5/195	disease causing (ClinVar)

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

dbSNP: rs1570520229; hg19: chr1-43282173;