chr8-66580273-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001080416.4(MYBL1):c.961T>C(p.Phe321Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000044 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
MYBL1
NM_001080416.4 missense
NM_001080416.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 3.85
Genes affected
MYBL1 (HGNC:7547): (MYB proto-oncogene like 1) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2630175).
BS2
?
High AC in GnomAd at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBL1 | NM_001080416.4 | c.961T>C | p.Phe321Leu | missense_variant | 9/16 | ENST00000522677.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBL1 | ENST00000522677.8 | c.961T>C | p.Phe321Leu | missense_variant | 9/16 | 1 | NM_001080416.4 | A1 | |
MYBL1 | ENST00000524176.2 | c.961T>C | p.Phe321Leu | missense_variant | 9/15 | 1 | P4 | ||
MYBL1 | ENST00000517885.5 | c.318-4140T>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152158Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000603 AC: 15AN: 248810Hom.: 0 AF XY: 0.0000741 AC XY: 10AN XY: 134970
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GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461546Hom.: 0 Cov.: 31 AF XY: 0.0000413 AC XY: 30AN XY: 727068
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74340
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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 | Jun 06, 2023 | The c.961T>C (p.F321L) alteration is located in exon 9 (coding exon 9) of the MYBL1 gene. This alteration results from a T to C substitution at nucleotide position 961, causing the phenylalanine (F) at amino acid position 321 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Loss of catalytic residue at F321 (P = 0.1121);Loss of catalytic residue at F321 (P = 0.1121);
MVP
MPC
ClinPred
T
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