NM_001127392.3:c.3301-592G>C

Variant names:

• chr11-61785208-G-C
• rs174537
• NM_001127392.3:c.3301-592G>C

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+2 Uncertain · Warm

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_001127392.3(MYRF):c.3301-592G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYRF NM_001127392.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.25
• Publications: 295 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]

MYRF Gene-Disease associations (from GenCC):

• cardiac-urogenital syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Ambry Genetics, ClinGen
• hyperopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• encephalitis/encephalopathy, mild, with reversible myelin vacuolization

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

TMEM258 (HGNC:1164): (transmembrane protein 258) Predicted to enable oligosaccharyltransferase complex binding activity. Involved in protein N-linked glycosylation. Acts upstream of or within protein secretion and response to endoplasmic reticulum stress. Located in endoplasmic reticulum and membrane. Part of oligosaccharyltransferase complex A and oligosaccharyltransferase complex B. [provided by Alliance of Genome Resources, Jun 2026]

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001127392.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MYRF NM_001127392.3	MANE Select	c.3301-592G>C	intron	Intron 25 of 26	Prot: NP_001120864.1 UniProt:
	MYRF NM_013279.4		c.3181-592G>C	intron	Intron 24 of 25	Prot: NP_037411.1 UniProt:

MYRF NM_001127392.3

MANE Select

HGVSc / HGVSpc.3301-592G>C

Exon rankIntron 25 of 26

intron

Prot: NP_001120864.1UniProt: Q9Y2G1-1

MYRF NM_013279.4

HGVSc / HGVSpc.3181-592G>C

Exon rankIntron 24 of 25

intron

Prot: NP_037411.1UniProt: Q9Y2G1-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	MYRF ENST00000278836.10	TSL:1MANE Select	c.3301-592G>C	intron	Intron 25 of 26	Prot: ENSP00000278836.4 UniProt:
	MYRF ENST00000265460.9	TSL:1	c.3181-592G>C	intron	Intron 24 of 25	Prot: ENSP00000265460.5 UniProt:
	MYRF ENST00000539361.1	TSL:1	n.3022G>C	non_coding_transcript_exon	Exon 2 of 2	Prot:

MYRF ENST00000278836.10

TSL:1MANE Select

HGVSc / HGVSpc.3301-592G>C

Exon rankIntron 25 of 26

intron

Prot: ENSP00000278836.4UniProt: Q9Y2G1-1

MYRF ENST00000265460.9

TSL:1

HGVSc / HGVSpc.3181-592G>C

Exon rankIntron 24 of 25

intron

Prot: ENSP00000265460.5UniProt: Q9Y2G1-2

MYRF ENST00000539361.1

TSL:1

HGVSc / HGVSpn.3022G>C

Exon rankExon 2 of 2

non_coding_transcript_exon

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:0
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	8.8
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.096
GPN-Star LLR	N/A	2.3
GPN-Star score	N/A	-2.0
PhyloP100	Benign	-5.2

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.010	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs174537;

hg19: chr11-61552680;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar