Variant 11-61783884-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001127392.3(MYRF):c.3153T>C(p.Ser1051Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,607,594 control chromosomes in the GnomAD database, including 102,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9107 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93760 hom. )

Consequence

MYRF
NM_001127392.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.41

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]

MYRF links:

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]

TMEM258 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 11-61783884-T-C is Benign according to our data. Variant chr11-61783884-T-C is described in ClinVar as [Benign]. Clinvar id is 1280429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3 link	c.3153T>C	p.Ser1051Ser	synonymous_variant	24/27	ENST00000278836.10	NP_001120864.1	Q9Y2G1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10 link	c.3153T>C	p.Ser1051Ser	synonymous_variant	24/27	1	NM_001127392.3	ENSP00000278836.4		Q9Y2G1-1

Frequencies

GnomAD3 genomes

AF:

0.325

AC:

49302

AN:

151824

Hom.:

9084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.233

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.342

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.380

AC:

91779

AN:

241624

Hom.:

20681

AF XY:

0.362

AC XY:

47274

AN XY:

130540

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.678

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.563

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.378

GnomAD4 exome

AF:

0.348

AC:

507169

AN:

1455652

Hom.:

93760

Cov.:

AF XY:

0.342

AC XY:

247698

AN XY:

723512

show subpopulations

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.662

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.462

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.424

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.325

AC:

49341

AN:

151942

Hom.:

9107

Cov.:

AF XY:

0.329

AC XY:

24445

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.506

Gnomad4 ASJ

AF:

0.293

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.342

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.332

Hom.:

19325

Bravo

AF:

0.331

Asia WGS

AF:

0.399

AC:

1387

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

7.0

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over