chr6-89098906-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_080743.5(SRSF12):c.458G>A(p.Arg153His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,696 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: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
SRSF12
NM_080743.5 missense
NM_080743.5 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 1.48
Genes affected
SRSF12 (HGNC:21220): (serine and arginine rich splicing factor 12) Enables RNA binding activity. Involved in mRNA 5'-splice site recognition and regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in cytoplasm and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.09267065).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRSF12 | NM_080743.5 | c.458G>A | p.Arg153His | missense_variant | 5/5 | ENST00000452027.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRSF12 | ENST00000452027.3 | c.458G>A | p.Arg153His | missense_variant | 5/5 | 1 | NM_080743.5 | P1 | |
SRSF12 | ENST00000524221.1 | n.740G>A | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
SRSF12 | ENST00000488604.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249024Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135082
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461682Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5AN XY: 727124
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74222
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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 | Feb 12, 2024 | The c.458G>A (p.R153H) alteration is located in exon 5 (coding exon 5) of the SRSF12 gene. This alteration results from a G to A substitution at nucleotide position 458, causing the arginine (R) at amino acid position 153 to be replaced by a histidine (H). 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
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of methylation at K155 (P = 0.1414);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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