NM_001167856.3:c.3713C>T

Variant names:

• chr12-123304637-G-A
• rs2048871911
• NM_001167856.3:c.3713C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001167856.3(SBNO1):​c.3713C>T​(p.Thr1238Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. T1238S) 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: 7.65
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2878306).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.3713C>T	p.Thr1238Ile	missense_variant	Exon 29 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.3710C>T	p.Thr1237Ile	missense_variant	Exon 29 of 32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.3713C>T	p.Thr1238Ile	missense_variant	Exon 29 of 32	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.3713C>T	p.Thr1238Ile	missense_variant	Exon 28 of 31	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.3710C>T	p.Thr1237Ile	missense_variant	Exon 29 of 32	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.90	L;.;L
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.3	D;D;.
REVEL	Uncertain	0.40
Sift	Benign	0.28	T;T;.
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0050	B;B;B
Vest4		0.63
MutPred		0.39		Loss of phosphorylation at T1238 (P = 0.0418);.;Loss of phosphorylation at T1238 (P = 0.0418);
MVP		0.39
MPC		0.75
ClinPred		0.98	D
GERP RS		6.2
Varity_R		0.44
gMVP		0.85
Mutation Taster		=70/30	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: rs2048871911; hg19: chr12-123789184;