11-66057317-G-C

Position:

• chr11-66057317-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006842.3(SF3B2):​c.719G>C​(p.Gly240Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SF3B2 NM_006842.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21537623).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3B2	NM_006842.3	c.719G>C	p.Gly240Ala	missense_variant	7/22	ENST00000322535.11	NP_006833.2
SF3B2	XM_005273726.5	c.716G>C	p.Gly239Ala	missense_variant	7/22		XP_005273783.1
SF3B2	XM_011544740.4	c.716G>C	p.Gly239Ala	missense_variant	7/22		XP_011543042.1
SF3B2	XM_017017144.3	c.713G>C	p.Gly238Ala	missense_variant	7/22		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11	c.719G>C	p.Gly240Ala	missense_variant	7/22	1	NM_006842.3	ENSP00000318861	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2024

The c.719G>C (p.G240A) alteration is located in exon 7 (coding exon 7) of the SF3B2 gene. This alteration results from a G to C substitution at nucleotide position 719, causing the glycine (G) at amino acid position 240 to be replaced by an alanine (A). 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	Benign	0.090
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.97
DEOGEN2	Benign	0.022	T;T;T;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.;.;.
MutationTaster	Benign	0.92	D;D
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.040	N;N;N;D;D
REVEL	Benign	0.080
Sift	Benign	0.070	T;T;D;T;T
Sift4G	Benign	0.59	T;T;T;T;T
Polyphen		0.82	.;P;.;.;.
Vest4		0.60
MutPred		0.31		.;Loss of sheet (P = 0.0315);.;.;.;
MVP		0.39
MPC		0.79
ClinPred		0.44	T
GERP RS		5.3
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Varity_R		0.048
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65824788;