12-123309736-T-A

Position:

• chr12-123309736-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001167856.3(SBNO1):​c.3416A>T​(p.Asn1139Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,444,606 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.03

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SBNO1	NM_001167856.3	c.3416A>T	p.Asn1139Ile	missense_variant	26/32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5	c.3413A>T	p.Asn1138Ile	missense_variant	26/32		NP_060653.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBNO1	ENST00000602398.3	c.3416A>T	p.Asn1139Ile	missense_variant	26/32	5	NM_001167856.3	ENSP00000473665.1
SBNO1	ENST00000420886.6	c.3416A>T	p.Asn1139Ile	missense_variant	25/31	1		ENSP00000387361.2
SBNO1	ENST00000267176.8	c.3413A>T	p.Asn1138Ile	missense_variant	26/32	5		ENSP00000267176.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444606 Hom.: 0 Cov.: 33 AF XY: 0.00000278 AC XY: 2 AN XY: 718306

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Aug 27, 2024

The c.3416A>T (p.N1139I) alteration is located in exon 25 (coding exon 25) of the SBNO1 gene. This alteration results from a A to T substitution at nucleotide position 3416, causing the asparagine (N) at amino acid position 1139 to be replaced by an isoleucine (I). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D;D;.
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.;N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.4	D;D;.
REVEL	Benign	0.13
Sift	Benign	0.11	T;T;.
Sift4G	Benign	0.10	T;T;T
Polyphen		0.93	P;P;P
Vest4		0.71
MVP		0.13
MPC		1.3
ClinPred		0.96	D
GERP RS		5.1
Varity_R		0.42
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-123794283;