12-123298029-C-G

Variant names:

• chr12-123298029-C-G
• rs114590549
• NM_001167856.3:c.3988G>C

Variant summary

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

The NM_001167856.3(SBNO1):​c.3988G>C​(p.Val1330Leu) 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. 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. V1330M) 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: 5.89
• Publications: 2 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=0.40690264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167856.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBNO1	NM_001167856.3	MANE Select	c.3988G>C	p.Val1330Leu	missense	Exon 31 of 32	NP_001161328.1	A3KN83-1
	SBNO1	NM_018183.5		c.3985G>C	p.Val1329Leu	missense	Exon 31 of 32	NP_060653.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SBNO1	ENST00000602398.3	TSL:5 MANE Select	c.3988G>C	p.Val1330Leu	missense	Exon 31 of 32	ENSP00000473665.1	A3KN83-1
	SBNO1	ENST00000420886.6	TSL:1	c.3988G>C	p.Val1330Leu	missense	Exon 30 of 31	ENSP00000387361.2	A3KN83-1
	SBNO1	ENST00000267176.8	TSL:5	c.3985G>C	p.Val1329Leu	missense	Exon 31 of 32	ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.016	T
Eigen	Benign	0.044
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.44	N
REVEL	Uncertain	0.33
Sift	Benign	0.65	T
Sift4G	Benign	0.65	T
Polyphen		0.029	B
Vest4		0.69
MutPred		0.36		Loss of MoRF binding (P = 0.101)
MVP		0.19
MPC		0.69
ClinPred		0.81	D
GERP RS		5.6
Varity_R		0.063
gMVP		0.64
Mutation Taster		=75/25	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: rs114590549; hg19: chr12-123782576;