Genetic Variant SBNO1:p.Phe1071Leu (chr12-123313629-A-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001167856.3(SBNO1):c.3211T>C(p.Phe1071Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3 link	c.3211T>C	p.Phe1071Leu	missense_variant	Exon 24 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 link	c.3208T>C	p.Phe1070Leu	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.3211T>C	p.Phe1071Leu	missense_variant	Exon 24 of 32	5	NM_001167856.3	ENSP00000473665.1	A3KN83-1
SBNO1	ENST00000420886.6 link	c.3211T>C	p.Phe1071Leu	missense_variant	Exon 23 of 31	1		ENSP00000387361.2	A3KN83-1
SBNO1	ENST00000267176.8 link	c.3208T>C	p.Phe1070Leu	missense_variant	Exon 24 of 32	5		ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1389118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694496

African (AFR)

AF:

0.00

AC:

AN:

31766

American (AMR)

AF:

0.00

AC:

AN:

42394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25210

East Asian (EAS)

AF:

0.00

AC:

AN:

39310

South Asian (SAS)

AF:

0.00

AC:

AN:

83020

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5460

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1051734

Other (OTH)

AF:

0.00

AC:

AN:

57768

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 15, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.3211T>C (p.F1071L) 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 3211, causing the phenylalanine (F) at amino acid position 1071 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

1.0

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.25

T;.;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

D;D;.

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.2

M;.;M

PhyloP100

9.2

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.8

D;D;.

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.88

P;P;P

Vest4

0.93

MutPred

0.66

Loss of ubiquitination at K1073 (P = 0.1231);.;Loss of ubiquitination at K1073 (P = 0.1231);

MVP

0.36

MPC

1.8

ClinPred

1.0

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.82

Mutation Taster

=33/67

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

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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