chr12-123298029-C-A

Variant names:

• chr12-123298029-C-A
• rs114590549
• NM_001167856.3:c.3988G>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.3988G>T​(p.Val1330Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.89
• 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=0.40581223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.3988G>T	p.Val1330Leu	missense_variant	Exon 31 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.3985G>T	p.Val1329Leu	missense_variant	Exon 31 of 32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.3988G>T	p.Val1330Leu	missense_variant	Exon 31 of 32	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.3988G>T	p.Val1330Leu	missense_variant	Exon 30 of 31	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.3985G>T	p.Val1329Leu	missense_variant	Exon 31 of 32	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461772 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;T
Eigen	Benign	0.044
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D;.
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.4	L;.;L
PhyloP100		5.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.44	N;N;.
REVEL	Uncertain	0.33
Sift	Benign	0.65	T;T;.
Sift4G	Benign	0.65	T;T;T
Polyphen		0.029	B;B;B
Vest4		0.69
MutPred		0.36		Loss of MoRF binding (P = 0.101);.;Loss of MoRF binding (P = 0.101);
MVP		0.18
MPC		0.69
ClinPred		0.81	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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;