chr12-57029188-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005379.4(MYO1A):​c.2949G>A​(p.Met983Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0310
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.13190433).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO1ANM_005379.4 linkc.2949G>A p.Met983Ile missense_variant Exon 27 of 28 ENST00000300119.8 NP_005370.1 Q9UBC5
MYO1ANM_001256041.2 linkc.2949G>A p.Met983Ile missense_variant Exon 28 of 29 NP_001242970.1 Q9UBC5B2R643
MYO1AXM_047428876.1 linkc.2949G>A p.Met983Ile missense_variant Exon 28 of 29 XP_047284832.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO1AENST00000300119.8 linkc.2949G>A p.Met983Ile missense_variant Exon 27 of 28 1 NM_005379.4 ENSP00000300119.3 Q9UBC5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251138
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461892
Hom.:
0
Cov.:
33
AF XY:
0.00000275
AC XY:
2
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2949G>A (p.M983I) alteration is located in exon 27 (coding exon 26) of the MYO1A gene. This alteration results from a G to A substitution at nucleotide position 2949, causing the methionine (M) at amino acid position 983 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.25
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
16
DANN
Benign
0.90
DEOGEN2
Benign
0.022
T;T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.46
.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.99
L;L
PrimateAI
Benign
0.48
T
PROVEAN
Benign
0.23
N;N
REVEL
Benign
0.043
Sift
Benign
0.37
T;T
Sift4G
Benign
0.35
T;T
Polyphen
0.0
B;B
Vest4
0.12
MutPred
0.75
Loss of MoRF binding (P = 0.1055);Loss of MoRF binding (P = 0.1055);
MVP
0.21
MPC
0.091
ClinPred
0.040
T
GERP RS
0.70
Varity_R
0.057
gMVP
0.24

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs749744206; hg19: chr12-57422972; API