11-66055118-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006842.3(SF3B2):c.301C>G(p.Pro101Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000427 in 1,404,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

SF3B2
NM_006842.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Publications

1 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17281833).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B2	NM_006842.3 link	c.301C>G	p.Pro101Ala	missense_variant	Exon 4 of 22	ENST00000322535.11	NP_006833.2	Q13435
SF3B2	XM_005273726.5 link	c.301C>G	p.Pro101Ala	missense_variant	Exon 4 of 22		XP_005273783.1
SF3B2	XM_011544740.4 link	c.301C>G	p.Pro101Ala	missense_variant	Exon 4 of 22		XP_011543042.1
SF3B2	XM_017017144.3 link	c.301C>G	p.Pro101Ala	missense_variant	Exon 4 of 22		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11 link	c.301C>G	p.Pro101Ala	missense_variant	Exon 4 of 22	1	NM_006842.3	ENSP00000318861.6		Q13435

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000935

AC:

AN:

213880

AF XY:

0.00000867

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000119

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000427

AC:

AN:

1404084

Hom.:

Cov.:

AF XY:

0.00000289

AC XY:

AN XY:

691510

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31856

American (AMR)

AF:

0.0000261

AC:

AN:

38318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23124

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38306

South Asian (SAS)

AF:

0.00

AC:

AN:

78460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51872

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5506

European-Non Finnish (NFE)

AF:

0.00000278

AC:

AN:

1078924

Other (OTH)

AF:

0.00

AC:

AN:

57718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Aug 04, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.301C>G (p.P101A) alteration is located in exon 4 (coding exon 4) of the SF3B2 gene. This alteration results from a C to G substitution at nucleotide position 301, causing the proline (P) at amino acid position 101 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

0.070

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.023

T;T;T;.;.;T

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.17

T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.4

.;L;.;.;.;.

PhyloP100

3.9

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.93

N;N;D;D;D;D

REVEL

Benign

0.15

Sift

Benign

0.19

T;T;T;T;T;.

Sift4G

Benign

0.10

T;T;D;D;T;D

Polyphen

0.99, 1.0

.;D;.;D;.;.

Vest4

0.34

MVP

0.42

MPC

1.1

ClinPred

0.28

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.047

gMVP

0.12

Mutation Taster

=84/16

polymorphism

(source)

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

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11-66055118-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over