1-42807460-T-C

Position:

• chr1-42807460-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_199342.4(SVBP):​c.155A>G​(p.Gln52Arg) 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: 4.04

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25890362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SVBP	NM_199342.4	c.155A>G	p.Gln52Arg	missense_variant	3/3	ENST00000372521.9	NP_955374.1
SVBP	XM_017001226.2	c.155A>G	p.Gln52Arg	missense_variant	3/3		XP_016856715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SVBP	ENST00000372521.9	c.155A>G	p.Gln52Arg	missense_variant	3/3	1	NM_199342.4	ENSP00000361599	P1
SVBP	ENST00000372522.5	c.155A>G	p.Gln52Arg	missense_variant	3/3	3		ENSP00000361600	P1
TMEM269	ENST00000421630.6	c.*196-1568T>C		intron_variant, NMD_transcript_variant		5		ENSP00000490287

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.155A>G (p.Q52R) alteration is located in exon 3 (coding exon 2) of the SVBP gene. This alteration results from a A to G substitution at nucleotide position 155, causing the glutamine (Q) at amino acid position 52 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	Benign	0.12
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.039	T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.67	.;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.29	T
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.16
Sift	Benign	0.12	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.98	D;D
Vest4		0.33
MutPred		0.13		Gain of MoRF binding (P = 0.0379);Gain of MoRF binding (P = 0.0379);
MVP		0.32
MPC		0.56
ClinPred		0.96	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.15

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: chr1-43273131;