11-61770248-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001127392.3(MYRF):c.463C>T(p.Pro155Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MYRF
NM_001127392.3 missense, splice_region
NM_001127392.3 missense, splice_region
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 3.27
Genes affected
MYRF (HGNC:1181): (myelin regulatory factor) This gene encodes a transcription factor that is required for central nervous system myelination and may regulate oligodendrocyte differentiation. It is thought to act by increasing the expression of genes that effect myelin production but may also directly promote myelin gene expression. Loss of a similar gene in mouse models results in severe demyelination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, MYRF
BP4
Computational evidence support a benign effect (MetaRNN=0.2526186).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYRF | NM_001127392.3 | c.463C>T | p.Pro155Ser | missense_variant, splice_region_variant | 5/27 | ENST00000278836.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYRF | ENST00000278836.10 | c.463C>T | p.Pro155Ser | missense_variant, splice_region_variant | 5/27 | 1 | NM_001127392.3 | P2 | |
MYRF | ENST00000265460.9 | c.436C>T | p.Pro146Ser | missense_variant, splice_region_variant | 5/26 | 1 | A2 | ||
MYRF | ENST00000675319.1 | c.106-1252C>T | intron_variant | ||||||
TMEM258 | ENST00000535042.1 | n.649-1475G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1452258Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 722028
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1452258
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
722028
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Encephalitis/encephalopathy, mild, with reversible myelin vacuolization Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 12, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0999);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at