rs727503322
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_005379.4(MYO1A):c.1270-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
MYO1A
NM_005379.4 splice_polypyrimidine_tract, intron
NM_005379.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001695
2
Clinical Significance
Conservation
PhyloP100: -0.0880
Genes affected
MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 12-57039284-G-A is Benign according to our data. Variant chr12-57039284-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 164595.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1A | NM_005379.4 | c.1270-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000300119.8 | |||
MYO1A | NM_001256041.2 | c.1270-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
MYO1A | XM_011538373.3 | c.1270-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
MYO1A | XM_047428876.1 | c.1270-10C>T | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1A | ENST00000300119.8 | c.1270-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005379.4 | P1 | |||
MYO1A | ENST00000442789.6 | c.1270-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
MYO1A | ENST00000476795.1 | n.157C>T | non_coding_transcript_exon_variant | 1/3 | 5 | ||||
MYO1A | ENST00000554234.5 | c.784-10C>T | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250790Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135558
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460132Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726508
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 16, 2014 | 1270-10C>T in intron 14 of MYO1A: This variant is not expected to have clinical significance because a C>T change at this position does not diverge from the spl ice consensus sequence and is therefore unlikely to impact splicing. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at