1-42807419-C-T

Variant names:

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

Variant summary

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

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

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=0.30851907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVBP	NM_199342.4	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 3	ENST00000372521.9	NP_955374.1
SVBP	XM_017001226.2	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 3		XP_016856715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVBP	ENST00000372521.9	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 3	1	NM_199342.4	ENSP00000361599.4
SVBP	ENST00000372522.5	c.196G>A	p.Glu66Lys	missense_variant	Exon 3 of 3	3		ENSP00000361600.1
TMEM269	ENST00000421630.6	n.*196-1609C>T		intron_variant	Intron 8 of 10	5		ENSP00000490287.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.196G>A (p.E66K) alteration is located in exon 3 (coding exon 2) of the SVBP gene. This alteration results from a G to A substitution at nucleotide position 196, causing the glutamic acid (E) at amino acid position 66 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	0.16
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T;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;T
MetaSVM	Uncertain	-0.26	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.26	T;T
Polyphen		1.0	D;D
Vest4		0.44
MutPred		0.25		Gain of methylation at E66 (P = 0.0042);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

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: chr1-43273090;