chr11-66057322-C-G

Variant names:

• chr11-66057322-C-G
• rs1185334474
• NM_006842.3:c.724C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006842.3(SF3B2):​c.724C>G​(p.Pro242Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P242S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: SF3B2 NM_006842.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.84
• Publications: 0 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]

ENSG00000255038 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.11260611).
• BS2: High AC in GnomAdExome4 at 38 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SF3B2	NM_006842.3	c.724C>G	p.Pro242Ala	missense_variant	Exon 7 of 22	ENST00000322535.11	NP_006833.2
SF3B2	XM_005273726.5	c.721C>G	p.Pro241Ala	missense_variant	Exon 7 of 22		XP_005273783.1
SF3B2	XM_011544740.4	c.721C>G	p.Pro241Ala	missense_variant	Exon 7 of 22		XP_011543042.1
SF3B2	XM_017017144.3	c.718C>G	p.Pro240Ala	missense_variant	Exon 7 of 22		XP_016872633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SF3B2	ENST00000322535.11	c.724C>G	p.Pro242Ala	missense_variant	Exon 7 of 22	1	NM_006842.3	ENSP00000318861.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250040 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000261 AC: 38 AN: 1456868 Hom.: 0 Cov.: 29 AF XY: 0.0000276 AC XY: 20 AN XY: 725144

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000343 AC: 38 AN: 1107476

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.023	T;T;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.031
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.84	T;T;T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	.;L;.;.;.
PhyloP100		1.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.8	N;N;N;D;N
REVEL	Benign	0.054
Sift	Uncertain	0.0090	D;D;D;D;D
Sift4G	Uncertain	0.030	D;D;T;T;T
Polyphen		0.012	.;B;.;.;.
Vest4		0.35
MutPred		0.19		.;Loss of relative solvent accessibility (P = 0.0306);.;.;.;
MVP		0.12
MPC		0.44
ClinPred		0.17	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.055
gMVP		0.15
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs1185334474; hg19: chr11-65824793;