12-123311090-A-G

Variant names:

• chr12-123311090-A-G
• rs773937558
• NM_001167856.3:c.3260T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001167856.3(SBNO1):​c.3260T>C​(p.Val1087Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1087G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.77
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.3260T>C	p.Val1087Ala	missense_variant	Exon 25 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.3257T>C	p.Val1086Ala	missense_variant	Exon 25 of 32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.3260T>C	p.Val1087Ala	missense_variant	Exon 25 of 32	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.3260T>C	p.Val1087Ala	missense_variant	Exon 24 of 31	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.3257T>C	p.Val1086Ala	missense_variant	Exon 25 of 32	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Benign	0.95
DEOGEN2	Benign	0.016	T;.;T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.059
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T;T;.
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N;.;N
PhyloP100		6.8
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.35	N;N;.
REVEL	Benign	0.21
Sift	Benign	0.78	T;T;.
Sift4G	Benign	0.76	T;T;T
Polyphen		0.059	B;B;B
Vest4		0.82
MutPred		0.50		Loss of stability (P = 0.0404);.;Loss of stability (P = 0.0404);
MVP		0.20
MPC		0.84
ClinPred		0.75	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.054
gMVP		0.59
Mutation Taster		=53/47	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

dbSNP: rs773937558; hg19: chr12-123795637;