Variant chr11-61766112-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_StrongBP6_Moderate

The NM_001127392.3(MYRF):c.289A>C(p.Thr97Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MYRF
NM_001127392.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.423

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:

MYRF (HGNC:):

MYRF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYRF. . Gene score misZ 3.2927 (greater than the threshold 3.09). Trascript score misZ 3.5469 (greater than threshold 3.09). GenCC has associacion of gene with encephalitis/encephalopathy, mild, with reversible myelin vacuolization, cardiac-urogenital syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.06397915).

BP6

Variant 11-61766112-A-C is Benign according to our data. Variant chr11-61766112-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2269114.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3 linkuse as main transcript	c.289A>C	p.Thr97Pro	missense_variant	3/27	ENST00000278836.10	NP_001120864.1	Q9Y2G1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYRF	ENST00000278836.10 linkuse as main transcript	c.289A>C	p.Thr97Pro	missense_variant	3/27	1	NM_001127392.3	ENSP00000278836.4	Q9Y2G1-1
MYRF	ENST00000265460.9 linkuse as main transcript	c.262A>C	p.Thr88Pro	missense_variant	3/26	1		ENSP00000265460.5	Q9Y2G1-2
MYRF	ENST00000537766.1 linkuse as main transcript	n.637A>C		non_coding_transcript_exon_variant	2/2	3
MYRF	ENST00000675319.1 linkuse as main transcript	c.-6A>C		upstream_gene_variant				ENSP00000502795.1	A0A6Q8PHM1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456482

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724810

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

1.5

DANN

Benign

0.21

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.050

Sift

Benign

0.19

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.058

B;B

Vest4

0.18

MutPred

0.14

Loss of phosphorylation at T97 (P = 0.0225);.;

MVP

0.14

MPC

0.14

ClinPred

0.13

GERP RS

-4.2

Varity_R

0.066

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over