12-123321694-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_001167856.3(SBNO1):c.2164G>A(p.Val722Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.965

Genes affected

SBNO1 (HGNC:22973): (strawberry notch homolog 1) Predicted to enable chromatin DNA binding activity and histone binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SBNO1
• BP4: Computational evidence support a benign effect (MetaRNN=0.027835697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.2164G>A	p.Val722Ile	missense_variant	17/32	ENST00000602398.3
SBNO1	NM_018183.5	c.2161G>A	p.Val721Ile	missense_variant	17/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.2164G>A	p.Val722Ile	missense_variant	17/32	5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.2164G>A	p.Val722Ile	missense_variant	16/31	1		P4
SBNO1	ENST00000267176.8	c.2161G>A	p.Val721Ile	missense_variant	17/32	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.2164G>A (p.V722I) alteration is located in exon 16 (coding exon 16) of the SBNO1 gene. This alteration results from a G to A substitution at nucleotide position 2164, causing the valine (V) at amino acid position 722 to be replaced by an isoleucine (I). 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	0.066
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	15
Dann	Benign	0.95
DEOGEN2	Benign	0.0073	T;.;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.83	T;T;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.028	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.070	N;N;.
REVEL	Benign	0.050
Sift	Benign	0.45	T;T;.
Sift4G	Benign	0.21	T;T;T
Polyphen		0.012	B;B;B
Vest4		0.070
MutPred		0.13		Gain of catalytic residue at V722 (P = 0.0624);.;Gain of catalytic residue at V722 (P = 0.0624);
MVP		0.093
MPC		0.55
ClinPred		0.16	T
GERP RS		0.072
Varity_R		0.032
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs372233667; hg19: chr12-123806241;