Variant 19-2247943-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007165.5(SF3A2):c.792G>A(p.Met264Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,311,434 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

SF3A2
NM_007165.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46

Variant links:

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]

SF3A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19104427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SF3A2	NM_007165.5 linkuse as main transcript	c.792G>A	p.Met264Ile	missense_variant	9/9	ENST00000221494.10	NP_009096.2	Q15428Q05DF2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SF3A2	ENST00000221494.10 linkuse as main transcript	c.792G>A	p.Met264Ile	missense_variant	9/9	1	NM_007165.5	ENSP00000221494.3		Q15428

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000550

AC:

AN:

181808

Hom.:

AF XY:

0.00

AC XY:

AN XY:

101752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000340

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000229

AC:

AN:

1311434

Hom.:

Cov.:

AF XY:

0.00000305

AC XY:

AN XY:

656514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000200

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000172

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.792G>A (p.M264I) alteration is located in exon 9 (coding exon 8) of the SF3A2 gene. This alteration results from a G to A substitution at nucleotide position 792, causing the methionine (M) at amino acid position 264 to be replaced by an isoleucine (I). 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

0.30

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.50

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.090

REVEL

Benign

0.075

Sift

Benign

0.23

Sift4G

Benign

0.46

Polyphen

0.16

Vest4

0.44

MutPred

0.26

Loss of glycosylation at P263 (P = 0.0735);

MVP

0.38

MPC

0.70

ClinPred

0.35

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.22

gMVP

0.035

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over