8-66566716-G-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001080416.4(MYBL1):c.1918C>G(p.Gln640Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,455,022 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: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
MYBL1
NM_001080416.4 missense
NM_001080416.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 4.66
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=0.16771817).
BS2
?
High AC in GnomAdExome at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBL1 | NM_001080416.4 | c.1918C>G | p.Gln640Glu | missense_variant | 14/16 | ENST00000522677.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBL1 | ENST00000522677.8 | c.1918C>G | p.Gln640Glu | missense_variant | 14/16 | 1 | NM_001080416.4 | A1 | |
MYBL1 | ENST00000524176.2 | c.1918C>G | p.Gln640Glu | missense_variant | 14/15 | 1 | P4 | ||
MYBL1 | ENST00000517885.5 | c.892C>G | p.Gln298Glu | missense_variant | 10/12 | 5 | |||
MYBL1 | ENST00000522419.1 | n.156C>G | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000574 AC: 14AN: 244080Hom.: 0 AF XY: 0.0000302 AC XY: 4AN XY: 132404
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1455022Hom.: 0 Cov.: 30 AF XY: 0.00000691 AC XY: 5AN XY: 723754
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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?
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4
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 | Dec 28, 2022 | The c.1918C>G (p.Q640E) alteration is located in exon 14 (coding exon 14) of the MYBL1 gene. This alteration results from a C to G substitution at nucleotide position 1918, causing the glutamine (Q) at amino acid position 640 to be replaced by a glutamic acid (E). 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
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MutPred
Gain of phosphorylation at S637 (P = 0.0839);.;Gain of phosphorylation at S637 (P = 0.0839);
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