Variant 11-61770270-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001127392.3(MYRF):c.485C>T(p.Thr162Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MYRF
NM_001127392.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

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:):

TMEM258 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYRF	NM_001127392.3 linkuse as main transcript	c.485C>T	p.Thr162Ile	missense_variant	5/27	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.485C>T	p.Thr162Ile	missense_variant	5/27	1	NM_001127392.3	ENSP00000278836.4	Q9Y2G1-1
MYRF	ENST00000265460.9 linkuse as main transcript	c.458C>T	p.Thr153Ile	missense_variant	5/26	1		ENSP00000265460.5	Q9Y2G1-2
MYRF	ENST00000675319.1 linkuse as main transcript	c.105-1230C>T		intron_variant				ENSP00000502795.1	A0A6Q8PHM1
TMEM258	ENST00000535042.1 linkuse as main transcript	n.649-1497G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

239944

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000941

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456518

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724388

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.485C>T (p.T162I) alteration is located in exon 5 (coding exon 5) of the MYRF gene. This alteration results from a C to T substitution at nucleotide position 485, causing the threonine (T) at amino acid position 162 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.83

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.024

D;D

Sift4G

Benign

0.23

T;T

Polyphen

1.0

D;D

Vest4

0.70

MutPred

0.27

Loss of glycosylation at T162 (P = 0.0468);.;

MVP

0.17

MPC

0.54

ClinPred

0.98

GERP RS

3.9

Varity_R

0.41

gMVP

0.54

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

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