1-37969716-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_006802.4(SF3A3):​c.1025A>G​(p.His342Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SF3A3
NM_006802.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11626375).
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SF3A3NM_006802.4 linkc.1025A>G p.His342Arg missense_variant Exon 13 of 17 ENST00000373019.5 NP_006793.1 Q12874
SF3A3NM_001320830.2 linkc.866A>G p.His289Arg missense_variant Exon 11 of 15 NP_001307759.1 B4DW90

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SF3A3ENST00000373019.5 linkc.1025A>G p.His342Arg missense_variant Exon 13 of 17 1 NM_006802.4 ENSP00000362110.4 Q12874
SF3A3ENST00000460925.1 linkn.570A>G non_coding_transcript_exon_variant Exon 3 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461864
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
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:
0.00000450
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
Jan 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1025A>G (p.H342R) alteration is located in exon 13 (coding exon 13) of the SF3A3 gene. This alteration results from a A to G substitution at nucleotide position 1025, causing the histidine (H) at amino acid position 342 to be replaced by an arginine (R). 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
0.084
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Benign
0.91
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.17
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-2.8
N
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
1.7
N
REVEL
Benign
0.14
Sift
Benign
0.64
T
Sift4G
Benign
0.58
T
Polyphen
0.0010
B
Vest4
0.38
MutPred
0.26
Gain of MoRF binding (P = 0.0135);
MVP
0.35
MPC
1.2
ClinPred
0.73
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.37
gMVP
0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-38435388; API