chr12-57029472-C-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_005379.4(MYO1A):c.2840G>T(p.Ser947Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000042 ( 1 hom. )
Consequence
MYO1A
NM_005379.4 missense
NM_005379.4 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 3.16
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28282592).
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1A | NM_005379.4 | c.2840G>T | p.Ser947Ile | missense_variant | 26/28 | ENST00000300119.8 | |
MYO1A | NM_001256041.2 | c.2840G>T | p.Ser947Ile | missense_variant | 27/29 | ||
MYO1A | XM_047428876.1 | c.2840G>T | p.Ser947Ile | missense_variant | 27/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1A | ENST00000300119.8 | c.2840G>T | p.Ser947Ile | missense_variant | 26/28 | 1 | NM_005379.4 | P1 | |
MYO1A | ENST00000442789.6 | c.2840G>T | p.Ser947Ile | missense_variant | 27/29 | 1 | P1 | ||
MYO1A | ENST00000477864.1 | n.403G>T | non_coding_transcript_exon_variant | 4/4 | 2 | ||||
MYO1A | ENST00000554234.5 | c.*285G>T | 3_prime_UTR_variant, NMD_transcript_variant | 22/24 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251302Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135812
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GnomAD4 exome AF: 0.0000424 AC: 62AN: 1461888Hom.: 1 Cov.: 33 AF XY: 0.0000578 AC XY: 42AN XY: 727248
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74362
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The c.2840G>T (p.S947I) alteration is located in exon 26 (coding exon 25) of the MYO1A gene. This alteration results from a G to T substitution at nucleotide position 2840, causing the serine (S) at amino acid position 947 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Loss of disorder (P = 0.0213);Loss of disorder (P = 0.0213);
MVP
MPC
0.36
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at