chr22-30342843-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_005877.6(SF3A1):c.688A>C(p.Lys230Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SF3A1
NM_005877.6 missense
NM_005877.6 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 7.66
Genes affected
SF3A1 (HGNC:10765): (splicing factor 3a subunit 1) This gene encodes a subunit of the splicing factor 3a protein complex. The splicing factor 3a heterotrimer is a component of the mature U2 small nuclear ribonucleoprotein particle (snRNP). U2 small nuclear ribonucleoproteins play a critical role in spliceosome assembly and pre-mRNA splicing. [provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SF3A1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3A1 | NM_005877.6 | c.688A>C | p.Lys230Gln | missense_variant | 5/16 | ENST00000215793.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3A1 | ENST00000215793.13 | c.688A>C | p.Lys230Gln | missense_variant | 5/16 | 1 | NM_005877.6 | P1 | |
SF3A1 | ENST00000471037.1 | n.259A>C | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
SF3A1 | ENST00000411423.1 | c.64-3664A>C | intron_variant, NMD_transcript_variant | 4 | |||||
SF3A1 | ENST00000447376.1 | c.*30A>C | 3_prime_UTR_variant, NMD_transcript_variant | 3/4 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250930Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135696
GnomAD3 exomes
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3
AN:
250930
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AN XY:
135696
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460882Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726860
GnomAD4 exome
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3
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1460882
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726860
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
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ExAC
?
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AC:
2
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 | Jun 03, 2022 | The c.688A>C (p.K230Q) alteration is located in exon 5 (coding exon 5) of the SF3A1 gene. This alteration results from a A to C substitution at nucleotide position 688, causing the lysine (K) at amino acid position 230 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of methylation at K230 (P = 0.0385);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at