11-61770355-A-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001127392.3(MYRF):c.570A>C(p.Pro190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.048 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYRF NM_001127392.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.59

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]

TMEM258 (HGNC:1164): (transmembrane protein 258) Involved in protein N-linked glycosylation. Located in endoplasmic reticulum. Part of oligosaccharyltransferase I complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-61770355-A-C is Benign according to our data. Variant chr11-61770355-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3037556.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.59 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYRF	NM_001127392.3	c.570A>C	p.Pro190=	synonymous_variant	5/27	ENST00000278836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYRF	ENST00000278836.10	c.570A>C	p.Pro190=	synonymous_variant	5/27	1	NM_001127392.3	P2
MYRF	ENST00000265460.9	c.543A>C	p.Pro181=	synonymous_variant	5/26	1		A2
MYRF	ENST00000675319.1	c.106-1145A>C		intron_variant
TMEM258	ENST00000535042.1	n.649-1582T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 706 AN: 41122 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.0381

Gnomad AMR AF: 0.00930

Gnomad ASJ AF: 0.0166

Gnomad EAS AF: 0.00326

Gnomad SAS AF: 0.0123

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0129

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0481 AC: 7959 AN: 165614 Hom.: 0 Cov.: 10 AF XY: 0.0494 AC XY: 4115 AN XY: 83290

Gnomad4 AFR exome AF: 0.0379

Gnomad4 AMR exome AF: 0.0918

Gnomad4 ASJ exome AF: 0.0406

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.0809

Gnomad4 FIN exome AF: 0.0746

Gnomad4 NFE exome AF: 0.0407

Gnomad4 OTH exome AF: 0.0438

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0171 AC: 704 AN: 41114 Hom.: 0 Cov.: 0 AF XY: 0.0150 AC XY: 313 AN XY: 20902

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.00927

Gnomad4 ASJ AF: 0.0166

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0183

Gnomad4 NFE AF: 0.0214

Gnomad4 OTH AF: 0.0129

Alfa AF: 0.0106 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

MYRF-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 28, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.1
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs780504743; hg19: chr11-61537827; COSMIC: COSV53886682; COSMIC: COSV53886682;