12-109397751-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_001101421.4(MYO1H):c.509C>T(p.Thr170Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000922 in 1,611,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00054 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00096 ( 0 hom. )
Consequence
MYO1H
NM_001101421.4 missense
NM_001101421.4 missense
Scores
13
2
2
Clinical Significance
Conservation
PhyloP100: 7.81
Genes affected
MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.878
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1H | NM_001101421.4 | c.509C>T | p.Thr170Met | missense_variant | 5/32 | ENST00000310903.10 | |
MYO1H | XM_011538223.3 | c.461C>T | p.Thr154Met | missense_variant | 6/34 | ||
MYO1H | XM_047428738.1 | c.461C>T | p.Thr154Met | missense_variant | 4/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1H | ENST00000310903.10 | c.509C>T | p.Thr170Met | missense_variant | 5/32 | 5 | NM_001101421.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000539 AC: 82AN: 152106Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.000566 AC: 140AN: 247198Hom.: 0 AF XY: 0.000574 AC XY: 77AN XY: 134114
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GnomAD4 exome AF: 0.000962 AC: 1404AN: 1459384Hom.: 0 Cov.: 29 AF XY: 0.000919 AC XY: 667AN XY: 725990
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GnomAD4 genome AF: 0.000539 AC: 82AN: 152224Hom.: 1 Cov.: 31 AF XY: 0.000497 AC XY: 37AN XY: 74402
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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 14, 2023 | The c.461C>T (p.T154M) alteration is located in exon 4 (coding exon 4) of the MYO1H gene. This alteration results from a C to T substitution at nucleotide position 461, causing the threonine (T) at amino acid position 154 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;H
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D
REVEL
Pathogenic
Sift
Pathogenic
.;D
Sift4G
Pathogenic
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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