12-123320725-A-G

Position:

• chr12-123320725-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001167856.3(SBNO1):​c.2465T>C​(p.Ile822Thr) 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. 14/21 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: 2.27

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052078903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.2465T>C	p.Ile822Thr	missense_variant	18/32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.2462T>C	p.Ile821Thr	missense_variant	18/32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.2465T>C	p.Ile822Thr	missense_variant	18/32	5	NM_001167856.3	ENSP00000473665	P4
SBNO1	ENST00000420886.6	c.2465T>C	p.Ile822Thr	missense_variant	17/31	1		ENSP00000387361	P4
SBNO1	ENST00000267176.8	c.2462T>C	p.Ile821Thr	missense_variant	18/32	5		ENSP00000267176	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 11, 2024

The c.2465T>C (p.I822T) alteration is located in exon 17 (coding exon 17) of the SBNO1 gene. This alteration results from a T to C substitution at nucleotide position 2465, causing the isoleucine (I) at amino acid position 822 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	0.090
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.0058	T;.;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.82	T;T;.
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.030	N;N;.
REVEL	Benign	0.047
Sift	Benign	0.39	T;T;.
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.31
MutPred		0.12		Gain of glycosylation at I822 (P = 0.0015);.;Gain of glycosylation at I822 (P = 0.0015);
MVP		0.082
MPC		0.85
ClinPred		0.34	T
GERP RS		5.7
Varity_R		0.053
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs1374318451; hg19: chr12-123805272;