Variant 19-1108380-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014963.3(SBNO2):c.3941A>T(p.Glu1314Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000527 in 1,137,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000053 ( 0 hom. )

Consequence

SBNO2
NM_014963.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

SBNO2 (HGNC:29158): (strawberry notch homolog 2) Predicted to enable chromatin DNA binding activity and histone binding activity. Involved in several processes, including cellular response to interleukin-6; macrophage activation involved in immune response; and negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SBNO2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28509462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SBNO2	NM_014963.3 linkuse as main transcript	c.3941A>T	p.Glu1314Val	missense_variant	32/32	ENST00000361757.8
SBNO2	NM_001100122.2 linkuse as main transcript	c.3770A>T	p.Glu1257Val	missense_variant	29/29
SBNO2	XM_047438466.1 linkuse as main transcript	c.2744A>T	p.Glu915Val	missense_variant	29/29
SBNO2	XM_011527804.4 linkuse as main transcript	c.*271A>T		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO2	ENST00000361757.8 linkuse as main transcript	c.3941A>T	p.Glu1314Val	missense_variant	32/32	1	NM_014963.3	P2	Q9Y2G9-1
SBNO2	ENST00000587024.5 linkuse as main transcript	c.3911A>T	p.Glu1304Val	missense_variant	32/32	2		A2
SBNO2	ENST00000438103.6 linkuse as main transcript	c.3770A>T	p.Glu1257Val	missense_variant	29/29	2		A2	Q9Y2G9-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000527

AC:

AN:

1137612

Hom.:

Cov.:

AF XY:

0.00000722

AC XY:

AN XY:

554288

show subpopulations

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:

0.00000424

Gnomad4 OTH exome

AF:

0.0000458

GnomAD4 genome

Cov.:

Alfa

AF:

0.000142

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2023

The c.3941A>T (p.E1314V) alteration is located in exon 32 (coding exon 31) of the SBNO2 gene. This alteration results from a A to T substitution at nucleotide position 3941, causing the glutamic acid (E) at amino acid position 1314 to be replaced by a valine (V). 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

0.48

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;.;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.71

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

0.70

N;N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.34

MutPred

0.61

Gain of catalytic residue at M1319 (P = 0.0236);.;.;

MVP

0.47

MPC

1.3

ClinPred

0.95

GERP RS

3.6

Varity_R

0.35

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over