19-1108380-T-A

Position:

• chr19-1108380-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06

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]

ACMG classification

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	Protein	UniProt
SBNO2	NM_014963.3	c.3941A>T	p.Glu1314Val	missense_variant	32/32	ENST00000361757.8	NP_055778.2
SBNO2	NM_001100122.2	c.3770A>T	p.Glu1257Val	missense_variant	29/29		NP_001093592.1
SBNO2	XM_047438466.1	c.2744A>T	p.Glu915Val	missense_variant	29/29		XP_047294422.1
SBNO2	XM_011527804.4	c.*271A>T		3_prime_UTR_variant	32/32		XP_011526106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SBNO2	ENST00000361757.8	c.3941A>T	p.Glu1314Val	missense_variant	32/32	1	NM_014963.3	ENSP00000354733.2
SBNO2	ENST00000587024.5	c.3911A>T	p.Glu1304Val	missense_variant	32/32	2		ENSP00000468520.1
SBNO2	ENST00000438103.6	c.3770A>T	p.Glu1257Val	missense_variant	29/29	2		ENSP00000400762.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000527 AC: 6 AN: 1137612 Hom.: 0 Cov.: 33 AF XY: 0.00000722 AC XY: 4 AN XY: 554288

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.: 33

Alfa AF: 0.000142 Hom.: 0

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

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	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.71	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.29	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	2.0	M;.;.
PrimateAI	Pathogenic	0.91	D
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	D
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

Other links and lift over

dbSNP: rs1229183062; hg19: chr19-1108379;