NM_001127392.3:c.227G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001127392.3(MYRF):c.227G>A(p.Ser76Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000212 in 1,601,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

MYRF
NM_001127392.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 4.46

Publications

0 publications found

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 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

MYRF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0125134885).

BP6

Variant 11-61766050-G-A is Benign according to our data. Variant chr11-61766050-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2366952.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00021 (32/152238) while in subpopulation NFE AF = 0.000279 (19/67996). AF 95% confidence interval is 0.000182. There are 0 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 32 AD,Unknown gene.

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.227G>A	p.Ser76Asn	missense	Exon 3 of 27	NP_001120864.1	Q9Y2G1-1
	MYRF	NM_013279.4		c.200G>A	p.Ser67Asn	missense	Exon 3 of 26	NP_037411.1	Q9Y2G1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYRF	ENST00000278836.10	TSL:1 MANE Select	c.227G>A	p.Ser76Asn	missense	Exon 3 of 27	ENSP00000278836.4	Q9Y2G1-1
MYRF	ENST00000265460.9	TSL:1	c.200G>A	p.Ser67Asn	missense	Exon 3 of 26	ENSP00000265460.5	Q9Y2G1-2
MYRF	ENST00000856811.1		c.227G>A	p.Ser76Asn	missense	Exon 3 of 27	ENSP00000526870.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000263

AC:

AN:

217110

AF XY:

0.000306

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000625

Gnomad NFE exome

AF:

0.000190

Gnomad OTH exome

AF:

0.000369

GnomAD4 exome

AF:

0.000212

AC:

307

AN:

1449488

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

160

AN XY:

721000

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33360

American (AMR)

AF:

0.0000914

AC:

AN:

43786

Ashkenazi Jewish (ASJ)

AF:

0.00278

AC:

AN:

25880

East Asian (EAS)

AF:

0.00

AC:

AN:

39408

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85600

European-Finnish (FIN)

AF:

0.0000213

AC:

AN:

46962

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.000188

AC:

209

AN:

1108760

Other (OTH)

AF:

0.000300

AC:

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000210

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41534

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

67996

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000268

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.078

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

M_CAP

Benign

0.017

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

PhyloP100

4.5

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.93

REVEL

Benign

0.032

Sift

Benign

0.17

Sift4G

Benign

0.26

Polyphen

0.65

Vest4

0.17

MVP

0.25

MPC

0.094

ClinPred

0.064

GERP RS

3.5

PromoterAI

0.013

Neutral

(source)

Varity_R

0.15

gMVP

0.15

Mutation Taster

=79/21

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over