19-1108796-T-C

Position:

• chr19-1108796-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014963.3(SBNO2):​c.3599A>G​(p.Asp1200Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000689 in 1,450,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SBNO2 NM_014963.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.04

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SBNO2	NM_014963.3	c.3599A>G	p.Asp1200Gly	missense_variant	31/32	ENST00000361757.8
SBNO2	NM_001100122.2	c.3428A>G	p.Asp1143Gly	missense_variant	28/29
SBNO2	XM_011527804.4	c.3599A>G	p.Asp1200Gly	missense_variant	31/32
SBNO2	XM_047438466.1	c.2402A>G	p.Asp801Gly	missense_variant	28/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SBNO2	ENST00000361757.8	c.3599A>G	p.Asp1200Gly	missense_variant	31/32	1	NM_014963.3	P2
SBNO2	ENST00000587024.5	c.3569A>G	p.Asp1190Gly	missense_variant	31/32	2		A2
SBNO2	ENST00000438103.6	c.3428A>G	p.Asp1143Gly	missense_variant	28/29	2		A2
SBNO2	ENST00000587673.5	n.1052A>G		non_coding_transcript_exon_variant	6/7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450976 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 722262

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Uncertain	0.36	D
MutationAssessor	Uncertain	2.3	M;.;.
MutationTaster	Benign	0.73	D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-4.5	D;D;.
REVEL	Uncertain	0.48
Sift	Uncertain	0.020	D;D;.
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.96	D;D;.
Vest4		0.34
MutPred		0.45		Loss of solvent accessibility (P = 0.1177);.;.;
MVP		0.62
MPC		1.0
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.51
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs909891603; hg19: chr19-1108795;