Genetic Variant ENST00000531041.1:n.201T>C (chr11-66052721-T-C) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The ENST00000531041.1(SF3B2):n.201T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SF3B2
ENST00000531041.1 non_coding_transcript_exon

Scores

Splicing: ADA: 0.9884

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.39

Publications

0 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_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

BayesDel_addAF computational evidence supports a deleterious effect, 0.221

PP5

Variant 11-66052721-T-C is Pathogenic according to our data. Variant chr11-66052721-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 3383153.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SF3B2	NM_006842.3 link	c.180+2T>C	splice_donor_variant, intron_variant	Intron 2 of 21	ENST00000322535.11	NP_006833.2	Q13435
SF3B2	XM_005273726.5 link	c.180+2T>C	splice_donor_variant, intron_variant	Intron 2 of 21		XP_005273783.1
SF3B2	XM_011544740.4 link	c.180+2T>C	splice_donor_variant, intron_variant	Intron 2 of 21		XP_011543042.1
SF3B2	XM_017017144.3 link	c.180+2T>C	splice_donor_variant, intron_variant	Intron 2 of 21		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11 link	c.180+2T>C		splice_donor_variant, intron_variant	Intron 2 of 21	1	NM_006842.3	ENSP00000318861.6		Q13435

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1414830

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701304

show subpopulations

African (AFR)

AF:

0.0000318

AC:

AN:

31414

American (AMR)

AF:

0.00

AC:

AN:

34352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22840

East Asian (EAS)

AF:

0.00

AC:

AN:

39396

South Asian (SAS)

AF:

0.00

AC:

AN:

78856

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51742

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092460

Other (OTH)

AF:

0.00

AC:

AN:

58252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Craniofacial microsomia 1

Pathogenic:1

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PVS1+PM2_Supporting+PM6_Supporting -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Benign

0.65

PhyloP100

1.4

GERP RS

5.1

PromoterAI

-0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=8/92

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.71

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.29

Position offset: -2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

ENST00000531041.1:n.201T>C

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