1-42807419-C-T

Variant names:

• chr1-42807419-C-T
• NM_199342.4:c.196G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_199342.4(SVBP):​c.196G>A​(p.Glu66Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SVBP NM_199342.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54
• 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: Uncertain_significance. The variant received 2 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=0.30851907).

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.196G>A	p.Glu66Lys	missense	Exon 3 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.196G>A	p.Glu66Lys	missense	Exon 3 of 3	ENSP00000361599.4	Q8N300
	SVBP	ENST00000372522.5	TSL:3	c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	ENSP00000361600.1	Q8N300
	SVBP	ENST00000881555.1		c.196G>A	p.Glu66Lys	missense	Exon 3 of 3	ENSP00000551614.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	-0.26	T
PhyloP100		5.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.25		Gain of methylation at E66 (P = 0.0042)
MVP		0.22
MPC		1.0
ClinPred		0.99	D
GERP RS		5.9
Varity_R		0.86
gMVP		0.16
Mutation Taster		=65/35	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: chr1-43273090;