NM_013451.4:c.6059T>C

Variant names:

• chr10-93310108-A-G
• NM_013451.4:c.6059T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_013451.4(MYOF):​c.6059T>C​(p.Val2020Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOF NM_013451.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

Genes affected

MYOF (HGNC:3656): (myoferlin) Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes. The protein contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length nature has not been determined. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.6059T>C	p.Val2020Ala	missense_variant	Exon 53 of 54	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.6059T>C	p.Val2020Ala	missense_variant	Exon 53 of 54	1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.6020T>C	p.Val2007Ala	missense_variant	Exon 52 of 53	1		ENSP00000351094.5
MYOF	ENST00000463743.5	n.*618T>C		non_coding_transcript_exon_variant	Exon 33 of 34	5		ENSP00000432708.1
MYOF	ENST00000463743.5	n.*618T>C		3_prime_UTR_variant	Exon 33 of 34	5		ENSP00000432708.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Feb 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYOF: PM2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	.;D
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.095	T;T
Polyphen		0.032	B;B
Vest4		0.84
MutPred		0.40		.;Loss of ubiquitination at K2017 (P = 0.0982);
MVP		0.82
MPC		0.27
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.48
gMVP		0.85

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: chr10-95069865;