19-1108802-G-C

Position:

• chr19-1108802-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014963.3(SBNO2):​c.3593C>G​(p.Thr1198Ser) 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: 33)
• Consequence: SBNO2 NM_014963.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.855

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO2	NM_014963.3	c.3593C>G	p.Thr1198Ser	missense_variant	31/32	ENST00000361757.8
SBNO2	NM_001100122.2	c.3422C>G	p.Thr1141Ser	missense_variant	28/29
SBNO2	XM_011527804.4	c.3593C>G	p.Thr1198Ser	missense_variant	31/32
SBNO2	XM_047438466.1	c.2396C>G	p.Thr799Ser	missense_variant	28/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO2	ENST00000361757.8	c.3593C>G	p.Thr1198Ser	missense_variant	31/32	1	NM_014963.3	P2
SBNO2	ENST00000587024.5	c.3563C>G	p.Thr1188Ser	missense_variant	31/32	2		A2
SBNO2	ENST00000438103.6	c.3422C>G	p.Thr1141Ser	missense_variant	28/29	2		A2
SBNO2	ENST00000587673.5	n.1046C>G		non_coding_transcript_exon_variant	6/7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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 30, 2021

The c.3593C>G (p.T1198S) alteration is located in exon 31 (coding exon 30) of the SBNO2 gene. This alteration results from a C to G substitution at nucleotide position 3593, causing the threonine (T) at amino acid position 1198 to be replaced by a serine (S). 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	0.68
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.084	D
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	0.86	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.7	D;D;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.017	D;D;.
Sift4G	Uncertain	0.045	D;T;T
Polyphen		1.0	D;D;.
Vest4		0.69
MutPred		0.53		Gain of disorder (P = 0.0367);.;.;
MVP		0.73
MPC		1.1
ClinPred		0.99	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.57
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1108801;