chr2-197402635-C-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 15P and 4B. PS1_Very_StrongPM1PM5PP2PP3PP5BS2
The NM_012433.4(SF3B1):c.1998G>C(p.Lys666Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K666E) has been classified as Likely pathogenic.
Frequency
Consequence
NM_012433.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SF3B1 | NM_012433.4 | c.1998G>C | p.Lys666Asn | missense_variant | 14/25 | ENST00000335508.11 | |
SF3B1 | XM_047443838.1 | c.1560G>C | p.Lys520Asn | missense_variant | 11/22 | ||
SF3B1 | XM_047443839.1 | c.1560G>C | p.Lys520Asn | missense_variant | 11/22 | ||
SF3B1 | XM_047443840.1 | c.1998G>C | p.Lys666Asn | missense_variant | 14/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SF3B1 | ENST00000335508.11 | c.1998G>C | p.Lys666Asn | missense_variant | 14/25 | 1 | NM_012433.4 | P1 | |
SF3B1 | ENST00000470268.2 | n.3882G>C | non_coding_transcript_exon_variant | 13/24 | 2 | ||||
SF3B1 | ENST00000652026.1 | c.*3065G>C | 3_prime_UTR_variant, NMD_transcript_variant | 14/25 | |||||
SF3B1 | ENST00000652738.1 | c.*2257G>C | 3_prime_UTR_variant, NMD_transcript_variant | 15/26 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251338Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135830
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461644Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25AN XY: 727112
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74340
ClinVar
Submissions by phenotype
Acute myeloid leukemia Pathogenic:2
Pathogenic, no assertion criteria provided | clinical testing | Sung Lab, Department of Medicine, Roswell Park Comprehensive Cancer Center | Jun 08, 2023 | - - |
Likely pathogenic, no assertion criteria provided | literature only | Database of Curated Mutations (DoCM) | Oct 02, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at