NM_013451.4:c.5860G>T

Variant names:

• chr10-93313049-C-A
• rs377745370
• NM_013451.4:c.5860G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013451.4(MYOF):​c.5860G>T​(p.Ala1954Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYOF NM_013451.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.108028024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.5860G>T	p.Ala1954Ser	missense_variant	Exon 51 of 54	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.5860G>T	p.Ala1954Ser	missense_variant	Exon 51 of 54	1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.5821G>T	p.Ala1941Ser	missense_variant	Exon 50 of 53	1		ENSP00000351094.5
MYOF	ENST00000463743.5	n.*419G>T		non_coding_transcript_exon_variant	Exon 31 of 34	5		ENSP00000432708.1
MYOF	ENST00000463743.5	n.*419G>T		3_prime_UTR_variant	Exon 31 of 34	5		ENSP00000432708.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.73	.;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.086
Sift	Benign	0.42	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.044	B;B
Vest4		0.27
MutPred		0.36		.;Loss of sheet (P = 0.0104);
MVP		0.70
MPC		0.15
ClinPred		0.21	T
GERP RS		1.4
Varity_R		0.087
gMVP		0.43

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

Other links and lift over

dbSNP: rs377745370; hg19: chr10-95072806;