19-2247804-C-T

Variant names:

• chr19-2247804-C-T
• rs200147511
• NM_007165.5:c.653C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_007165.5(SF3A2):​c.653C>T​(p.Pro218Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000777 in 1,609,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: SF3A2 NM_007165.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02
• Publications: 0 publications found

Genes affected

SF3A2 (HGNC:10766): (splicing factor 3a subunit 2) This gene encodes subunit 2 of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer includes subunits 1, 2 and 3 and is necessary for the in vitro conversion of 15S U2 snRNP into an active 17S particle that performs pre-mRNA splicing. Subunit 2 interacts with subunit 1 through its amino-terminus while the single zinc finger domain of subunit 2 plays a role in its binding to the 15S U2 snRNP. Subunit 2 may also function independently of its RNA splicing function as a microtubule-binding protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009569347).
• BS2: High AC in GnomAd4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007165.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A2	NM_007165.5	MANE Select	c.653C>T	p.Pro218Leu	missense	Exon 9 of 9	NP_009096.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SF3A2	ENST00000221494.10	TSL:1 MANE Select	c.653C>T	p.Pro218Leu	missense	Exon 9 of 9	ENSP00000221494.3	Q15428
	SF3A2	ENST00000866932.1		c.755C>T	p.Pro252Leu	missense	Exon 9 of 9	ENSP00000536991.1
	SF3A2	ENST00000866930.1		c.653C>T	p.Pro218Leu	missense	Exon 10 of 10	ENSP00000536989.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152030 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000391 AC: 95 AN: 242910 AF XY: 0.000308

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00270

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000782 AC: 114 AN: 1457642 Hom.: 0 Cov.: 33 AF XY: 0.0000717 AC XY: 52 AN XY: 725336

African (AFR) AF: 0.0000598 AC: 2 AN: 33460

American (AMR) AF: 0.00226 AC: 101 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000990 AC: 11 AN: 1111096

Other (OTH) AF: 0.00 AC: 0 AN: 60294

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 152030 Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4 AN XY: 74246

African (AFR) AF: 0.0000483 AC: 2 AN: 41370

American (AMR) AF: 0.000458 AC: 7 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67964

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000234

ExAC AF: 0.000248 AC: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.085
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		5.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.10
Sift	Benign	0.15	T
Sift4G	Uncertain	0.056	T
Polyphen		0.0070	B
Vest4		0.25
MutPred		0.34		Loss of catalytic residue at P217 (P = 0.0116)
MVP		0.15
MPC		0.64
ClinPred		0.13	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.11
gMVP		0.058
Mutation Taster		=87/13	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: rs200147511; hg19: chr19-2247803; COSMIC: COSV99677908; COSMIC: COSV99677908;