chr11-61765969-ACATCT-A

Variant names:

• chr11-61765969-ACATCT-A
• NM_001127392.3:c.148_152delATCTC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001127392.3(MYRF):​c.148_152delATCTC​(p.Ile50CysfsTer74) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYRF NM_001127392.3 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.92

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]

ACMG classification

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
• PP5: Variant 11-61765969-ACATCT-A is Pathogenic according to our data. Variant chr11-61765969-ACATCT-A is described in ClinVar as [Pathogenic]. Clinvar id is 3772320.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.148_152delATCTC	p.Ile50CysfsTer74	frameshift_variant	Exon 3 of 27	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.148_152delATCTC	p.Ile50CysfsTer74	frameshift_variant	Exon 3 of 27	1	NM_001127392.3	ENSP00000278836.4
MYRF	ENST00000265460.9	c.121_125delATCTC	p.Ile41CysfsTer74	frameshift_variant	Exon 3 of 26	1		ENSP00000265460.5
MYRF	ENST00000537766.1	n.496_500delATCTC		non_coding_transcript_exon_variant	Exon 2 of 2	3
MYRF	ENST00000675319.1	c.-148_-144delCATCT		upstream_gene_variant				ENSP00000502795.1

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: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYRF: PVS1, PS2, PM2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-61533441;