chr11-61765969-ACATCT-A

Variant names:

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

Variant summary

Our verdict is Pathogenic. The variant received 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 (★). Synonymous variant affecting the same amino acid position (i.e. I50I) has been classified as Likely benign. 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
• Publications: 0 publications found

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]

MYRF Gene-Disease associations (from GenCC):

• cardiac-urogenital syndrome

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• hyperopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• encephalitis/encephalopathy, mild, with reversible myelin vacuolization

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 3772320.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127392.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	NM_001127392.3	MANE Select	c.148_152delATCTC	p.Ile50CysfsTer74	frameshift	Exon 3 of 27	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.121_125delATCTC	p.Ile41CysfsTer74	frameshift	Exon 3 of 26	NP_037411.1	Q9Y2G1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	ENST00000278836.10	TSL:1 MANE Select	c.148_152delATCTC	p.Ile50CysfsTer74	frameshift	Exon 3 of 27	ENSP00000278836.4	Q9Y2G1-1
	MYRF	ENST00000265460.9	TSL:1	c.121_125delATCTC	p.Ile41CysfsTer74	frameshift	Exon 3 of 26	ENSP00000265460.5	Q9Y2G1-2
	MYRF	ENST00000856811.1		c.148_152delATCTC	p.Ile50CysfsTer74	frameshift	Exon 3 of 27	ENSP00000526870.1

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

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

Other links and lift over

hg19: chr11-61533441;