11-66055135-G-C

Variant names:

• chr11-66055135-G-C
• rs756928979
• NM_006842.3:c.318G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006842.3(SF3B2):​c.318G>C​(p.Pro106Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SF3B2 NM_006842.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29

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

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.014).
• BP6: Variant 11-66055135-G-C is Benign according to our data. Variant chr11-66055135-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2578660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.29 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B2	NM_006842.3	c.318G>C	p.Pro106Pro	synonymous_variant	Exon 4 of 22	ENST00000322535.11	NP_006833.2
SF3B2	XM_005273726.5	c.318G>C	p.Pro106Pro	synonymous_variant	Exon 4 of 22		XP_005273783.1
SF3B2	XM_011544740.4	c.318G>C	p.Pro106Pro	synonymous_variant	Exon 4 of 22		XP_011543042.1
SF3B2	XM_017017144.3	c.318G>C	p.Pro106Pro	synonymous_variant	Exon 4 of 22		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11	c.318G>C	p.Pro106Pro	synonymous_variant	Exon 4 of 22	1	NM_006842.3	ENSP00000318861.6

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 17 AN: 144190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000498

Gnomad AMI AF: 0.00116

Gnomad AMR AF: 0.000137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000700

Gnomad SAS AF: 0.000999

Gnomad FIN AF: 0.000220

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000458

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000221 AC: 237 AN: 1070404 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 121 AN XY: 530134

Gnomad4 AFR exome AF: 0.000384 AC: 9 AN: 23440

Gnomad4 AMR exome AF: 0.000271 AC: 9 AN: 33216

Gnomad4 ASJ exome AF: 0.000734 AC: 11 AN: 14996

Gnomad4 EAS exome AF: 0.000592 AC: 10 AN: 16882

Gnomad4 SAS exome AF: 0.0000133 AC: 1 AN: 75044

Gnomad4 FIN exome AF: 0.000413 AC: 14 AN: 33894

Gnomad4 NFE exome AF: 0.000200 AC: 166 AN: 829068

Gnomad4 Remaining exome AF: 0.000403 AC: 16 AN: 39722

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000118 AC: 17 AN: 144332 Hom.: 0 Cov.: 32 AF XY: 0.0000711 AC XY: 5 AN XY: 70300

Gnomad4 AFR AF: 0.0000497 AC: 0.0000496746 AN: 0.0000496746

Gnomad4 AMR AF: 0.000137 AC: 0.000136668 AN: 0.000136668

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.000700 AC: 0.00070028 AN: 0.00070028

Gnomad4 SAS AF: 0.000996 AC: 0.00099552 AN: 0.00099552

Gnomad4 FIN AF: 0.000220 AC: 0.000219829 AN: 0.000219829

Gnomad4 NFE AF: 0.0000458 AC: 0.0000458127 AN: 0.0000458127

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Genomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SF3B2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.61
DANN	Benign	0.56
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs756928979; hg19: chr11-65822606;