11-61766100-C-T

Variant names:

• chr11-61766100-C-T
• NM_001127392.3:c.277C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001127392.3(MYRF):​c.277C>T​(p.Pro93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P93L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYRF NM_001127392.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.59

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the MYRF gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 14 curated benign missense variants. Gene score misZ: 3.2927 (above the threshold of 3.09). Trascript score misZ: 3.5469 (above the threshold of 3.09). GenCC associations: The gene is linked to encephalitis/encephalopathy, mild, with reversible myelin vacuolization, cardiac-urogenital syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.16919807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYRF	NM_001127392.3	c.277C>T	p.Pro93Ser	missense_variant	Exon 3 of 27	ENST00000278836.10	NP_001120864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYRF	ENST00000278836.10	c.277C>T	p.Pro93Ser	missense_variant	Exon 3 of 27	1	NM_001127392.3	ENSP00000278836.4
MYRF	ENST00000265460.9	c.250C>T	p.Pro84Ser	missense_variant	Exon 3 of 26	1		ENSP00000265460.5
MYRF	ENST00000537766.1	n.625C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3
MYRF	ENST00000675319.1	c.-18C>T		upstream_gene_variant				ENSP00000502795.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 11, 2021

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.2	N;D
REVEL	Benign	0.074
Sift	Uncertain	0.013	D;D
Sift4G	Benign	0.18	T;T
Polyphen		0.95	P;B
Vest4		0.35
MutPred		0.34		Gain of phosphorylation at P93 (P = 0.0327);.;
MVP		0.17
MPC		0.19
ClinPred		0.80	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.14
gMVP		0.33

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.

Other links and lift over

hg19: chr11-61533572;