chr11-61766173-GCACCGGGCCCCCCATC-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP2PP5

The NM_001127392.3(MYRF):​c.350_366delGCACCGGGCCCCCCATCinsT​(p.Gly117ValfsTer31) variant causes a frameshift, missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

MYRF
NM_001127392.3 frameshift, missense

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.58
Variant links:
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 Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the MYRF gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 14 curated benign missense variants. Gene score misZ: 3.2927 (above the threshold of 3.09). Trascript score misZ: 3.5469 (above the threshold of 3.09). GenCC associations: The gene is linked to encephalitis/encephalopathy, mild, with reversible myelin vacuolization, cardiac-urogenital syndrome.
PP5
Variant 11-61766173-GCACCGGGCCCCCCATC-T is Pathogenic according to our data. Variant chr11-61766173-GCACCGGGCCCCCCATC-T is described in ClinVar as [Pathogenic]. Clinvar id is 635276.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYRFNM_001127392.3 linkc.350_366delGCACCGGGCCCCCCATCinsT p.Gly117ValfsTer31 frameshift_variant, missense_variant Exon 3 of 27 ENST00000278836.10 NP_001120864.1 Q9Y2G1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYRFENST00000278836.10 linkc.350_366delGCACCGGGCCCCCCATCinsT p.Gly117ValfsTer31 frameshift_variant, missense_variant Exon 3 of 27 1 NM_001127392.3 ENSP00000278836.4 Q9Y2G1-1
MYRFENST00000265460.9 linkc.323_339delGCACCGGGCCCCCCATCinsT p.Gly108ValfsTer31 frameshift_variant, missense_variant Exon 3 of 26 1 ENSP00000265460.5 Q9Y2G1-2
MYRFENST00000675319.1 linkc.56_72delGCACCGGGCCCCCCATCinsT p.Gly19LysfsTer916 frameshift_variant, missense_variant Exon 1 of 23 ENSP00000502795.1 A0A6Q8PHM1
MYRFENST00000537766.1 linkn.698_714delGCACCGGGCCCCCCATCinsT non_coding_transcript_exon_variant Exon 2 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Cardiac-urogenital syndrome Pathogenic:1
Apr 06, 2019
Daryl Scott Lab, Baylor College of Medicine
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1565286228; hg19: chr11-61533645; API