NM_006842.3:c.2099A>G

Variant names:

• chr11-66063413-A-G
• rs1057519960
• NM_006842.3:c.2099A>G
• SF3B2 p.Glu700Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006842.3(SF3B2):​c.2099A>G​(p.Glu700Gly) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SF3B2 NM_006842.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.44
• Publications: 1 publications found

Genes affected

SF3B2 (HGNC:10769): (splicing factor 3b subunit 2) This gene encodes subunit 2 of the splicing factor 3b protein complex. Splicing factor 3b, together with splicing factor 3a and a 12S RNA unit, forms the U2 small nuclear ribonucleoproteins complex (U2 snRNP). The splicing factor 3b/3a complex binds pre-mRNA upstream of the intron's branch site in a sequence-independent manner and may anchor the U2 snRNP to the pre-mRNA. Splicing factor 3b is also a component of the minor U12-type spliceosome. Subunit 2 associates with pre-mRNA upstream of the branch site at the anchoring site. Subunit 2 also interacts directly with subunit 4 of the splicing factor 3b complex. Subunit 2 is a highly hydrophilic protein with a proline-rich N-terminus and a glutamate-rich stretch in the C-terminus. [provided by RefSeq, Jul 2008]

SF3B2 Gene-Disease associations (from GenCC):

• craniofacial microsomia 1

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

ENSG00000255038 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21071798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006842.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3B2	NM_006842.3	MANE Select	c.2099A>G	p.Glu700Gly	missense	Exon 18 of 22	NP_006833.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3B2	ENST00000322535.11	TSL:1 MANE Select	c.2099A>G	p.Glu700Gly	missense	Exon 18 of 22	ENSP00000318861.6	Q13435
	SF3B2	ENST00000934121.1		c.2207A>G	p.Glu736Gly	missense	Exon 17 of 21	ENSP00000604180.1
	SF3B2	ENST00000893573.1		c.2168A>G	p.Glu723Gly	missense	Exon 18 of 22	ENSP00000563632.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.91	L
PhyloP100		8.4
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.36
Sift	Benign	0.27	T
Sift4G	Benign	0.31	T
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.2
Varity_R		0.34
gMVP		0.76
Mutation Taster		=23/77	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1057519960;

hg19: chr11-65830884;