12-123309502-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2 BS2

The NM_001167856.3(SBNO1):c.3524T>C(p.Val1175Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,460,656 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SBNO1 NM_001167856.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.06

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 -3 ACMG points.

• PP2: Missense variant where missense usually causes diseases, SBNO1
• BS2: High AC in GnomAdExome at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO1	NM_001167856.3	c.3524T>C	p.Val1175Ala	missense_variant	27/32	ENST00000602398.3
SBNO1	NM_018183.5	c.3521T>C	p.Val1174Ala	missense_variant	27/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO1	ENST00000602398.3	c.3524T>C	p.Val1175Ala	missense_variant	27/32	5	NM_001167856.3	P4
SBNO1	ENST00000420886.6	c.3524T>C	p.Val1175Ala	missense_variant	26/31	1		P4
SBNO1	ENST00000267176.8	c.3521T>C	p.Val1174Ala	missense_variant	27/32	5		A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000239 AC: 6 AN: 251300 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135856

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1460656 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726762

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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

Dec 14, 2023

The c.3524T>C (p.V1175A) alteration is located in exon 26 (coding exon 26) of the SBNO1 gene. This alteration results from a T to C substitution at nucleotide position 3524, causing the valine (V) at amino acid position 1175 to be replaced by an alanine (A). 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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.0025	T
BayesDel_noAF	Uncertain	-0.040
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.054	T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;D;.
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.7	M;.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.9	N;N;.
REVEL	Uncertain	0.37
Sift	Benign	0.056	T;D;.
Sift4G	Uncertain	0.040	D;D;D
Polyphen		0.82	P;P;P
Vest4		0.87
MutPred		0.54		Gain of disorder (P = 0.0649);.;Gain of disorder (P = 0.0649);
MVP		0.31
MPC		0.88
ClinPred		0.52	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.79

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: rs775834999; hg19: chr12-123794049;