dbSNP rs775834999: SBNO1:p.Val1175Gly (chr12-123309502-A-C) – 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.3524T>G(p.Val1175Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V1175A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SBNO1
NM_001167856.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.06

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, 0.823

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SBNO1	NM_001167856.3 link	c.3524T>G	p.Val1175Gly	missense_variant	Exon 27 of 32	ENST00000602398.3	NP_001161328.1
SBNO1	NM_018183.5 link	c.3521T>G	p.Val1174Gly	missense_variant	Exon 27 of 32		NP_060653.3	A3KN83-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SBNO1	ENST00000602398.3 link	c.3524T>G	p.Val1175Gly	missense_variant	Exon 27 of 32	5	NM_001167856.3	ENSP00000473665.1	A3KN83-1
SBNO1	ENST00000420886.6 link	c.3524T>G	p.Val1175Gly	missense_variant	Exon 26 of 31	1		ENSP00000387361.2	A3KN83-1
SBNO1	ENST00000267176.8 link	c.3521T>G	p.Val1174Gly	missense_variant	Exon 27 of 32	5		ENSP00000267176.4	A3KN83-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460656

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726762

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110918

Other (OTH)

AF:

0.00

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.;T

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;.

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.82

D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.7

M;.;M

PhyloP100

9.1

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-4.2

D;D;.

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.96

P;D;P

Vest4

0.72

MutPred

0.60

Gain of disorder (P = 0.0145);.;Gain of disorder (P = 0.0145);

MVP

0.71

MPC

1.3

ClinPred

1.0

GERP RS

5.0

Varity_R

0.83

gMVP

0.93

Mutation Taster

=45/55

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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rs775834999

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over