chr11-61783884-T-A

Variant names:

• chr11-61783884-T-A
• rs174535
• NM_001127392.3:c.3153T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001127392.3(MYRF):​c.3153T>A​(p.Ser1051Arg) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1051S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYRF NM_001127392.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• Publications: 153 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	NM_001127392.3	MANE Select	c.3153T>A	p.Ser1051Arg	missense	Exon 24 of 27	NP_001120864.1
	MYRF	NM_013279.4		c.3033T>A	p.Ser1011Arg	missense	Exon 23 of 26	NP_037411.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYRF	ENST00000278836.10	TSL:1 MANE Select	c.3153T>A	p.Ser1051Arg	missense	Exon 24 of 27	ENSP00000278836.4
	MYRF	ENST00000265460.9	TSL:1	c.3033T>A	p.Ser1011Arg	missense	Exon 23 of 26	ENSP00000265460.5
	MYRF	ENST00000539361.1	TSL:1	n.1698T>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.61	T
PhyloP100		2.4
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.088	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.24		Loss of glycosylation at S1051 (P = 0.0483)
MVP		0.55
MPC		1.1
ClinPred		0.97	D
GERP RS		1.3
Varity_R		0.56
gMVP		0.98
Mutation Taster		=63/37	polymorphism

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

Other links and lift over

dbSNP: rs174535; hg19: chr11-61551356;