1-37987791-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006802.4(SF3A3):​c.190A>G​(p.Lys64Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,461,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SF3A3
NM_006802.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
Variant links:
Genes affected
SF3A3 (HGNC:10767): (splicing factor 3a subunit 3) This gene encodes subunit 3 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 3 interacts with subunit 1 through its amino-terminus while the zinc finger domain of subunit 3 plays a role in its binding to the 15S U2 snRNP. This gene has a pseudogene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.39200616).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SF3A3NM_006802.4 linkc.190A>G p.Lys64Glu missense_variant Exon 3 of 17 ENST00000373019.5 NP_006793.1 Q12874
SF3A3NM_001320830.2 linkc.144+1757A>G intron_variant Intron 2 of 14 NP_001307759.1 B4DW90

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SF3A3ENST00000373019.5 linkc.190A>G p.Lys64Glu missense_variant Exon 3 of 17 1 NM_006802.4 ENSP00000362110.4 Q12874

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000890
AC:
13
AN:
1461066
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
726910
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:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.190A>G (p.K64E) alteration is located in exon 3 (coding exon 3) of the SF3A3 gene. This alteration results from a A to G substitution at nucleotide position 190, causing the lysine (K) at amino acid position 64 to be replaced by a glutamic acid (E). 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
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.024
T
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.64
N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.20
Sift
Benign
0.26
T
Sift4G
Benign
0.65
T
Polyphen
0.96
P
Vest4
0.51
MutPred
0.28
Loss of ubiquitination at K64 (P = 0.003);
MVP
0.70
MPC
1.4
ClinPred
0.78
D
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.52
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-38453463; API