Genetic Variant SBNO1:p.Phe1072Leu (chr12-123313626-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001167856.3(SBNO1):c.3214T>C(p.Phe1072Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,184 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.23

Publications

0 publications found

Variant links:

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]

SBNO1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3 link	c.3214T>C	p.Phe1072Leu	missense_variant	Exon 24 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 link	c.3211T>C	p.Phe1071Leu	missense_variant	Exon 24 of 32		NP_060653.3	A3KN83-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SBNO1	ENST00000602398.3 link	c.3214T>C	p.Phe1072Leu	missense_variant	Exon 24 of 32	5	NM_001167856.3	ENSP00000473665.1	A3KN83-1
SBNO1	ENST00000420886.6 link	c.3214T>C	p.Phe1072Leu	missense_variant	Exon 23 of 31	1		ENSP00000387361.2	A3KN83-1
SBNO1	ENST00000267176.8 link	c.3211T>C	p.Phe1071Leu	missense_variant	Exon 24 of 32	5		ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.22e-7

AC:

AN:

1385184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

692908

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31754

American (AMR)

AF:

0.00

AC:

AN:

42804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25240

East Asian (EAS)

AF:

0.00

AC:

AN:

39300

South Asian (SAS)

AF:

0.00

AC:

AN:

83158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047470

Other (OTH)

AF:

0.0000174

AC:

AN:

57598

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000625

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3214T>C (p.F1072L) alteration is located in exon 23 (coding exon 23) of the SBNO1 gene. This alteration results from a T to C substitution at nucleotide position 3214, causing the phenylalanine (F) at amino acid position 1072 to be replaced by a leucine (L). 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

0.95

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;.

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M

PhyloP100

9.2

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.7

D;D;.

REVEL

Benign

0.28

Sift

Benign

0.14

T;T;.

Sift4G

Uncertain

0.035

D;D;D

Polyphen

0.57

P;P;P

Vest4

0.83

MutPred

0.42

Loss of methylation at K1073 (P = 0.0347);.;Loss of methylation at K1073 (P = 0.0347);

MVP

0.22

MPC

0.98

ClinPred

0.98

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.75

Mutation Taster

=29/71

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over