12-123313638-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001167856.3(SBNO1):c.3202C>A(p.Pro1068Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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 Uncertain_significance. 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=0.08138251).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.3202C>A	p.Pro1068Thr	missense_variant	24/32	ENST00000602398.3
SBNO1	NM_018183.5	c.3199C>A	p.Pro1067Thr	missense_variant	24/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.3202C>A	p.Pro1068Thr	missense_variant	24/32	5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.3202C>A	p.Pro1068Thr	missense_variant	23/31	1		P4
SBNO1	ENST00000267176.8	c.3199C>A	p.Pro1067Thr	missense_variant	24/32	5		A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1420128 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 708666

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Jul 11, 2023

The c.3202C>A (p.P1068T) alteration is located in exon 23 (coding exon 23) of the SBNO1 gene. This alteration results from a C to A substitution at nucleotide position 3202, causing the proline (P) at amino acid position 1068 to be replaced by a threonine (T). 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	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	23
Dann	Uncertain	0.98
DEOGEN2	Benign	0.030	T;.;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;D;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.081	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L;.;L
MutationTaster	Benign	0.99	D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.093
Sift	Benign	0.14	T;T;.
Sift4G	Benign	0.14	T;T;T
Polyphen		0.14	B;B;B
Vest4		0.49
MutPred		0.31		Gain of phosphorylation at P1068 (P = 0.0152);.;Gain of phosphorylation at P1068 (P = 0.0152);
MVP		0.068
MPC		0.84
ClinPred		0.46	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
gMVP		0.33

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: chr12-123798185;