chr2-191393083-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 5P and 4B. PP2PP3_StrongBS2
The NM_001130158.3(MYO1B):c.2087T>C(p.Leu696Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,613,334 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 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 1 hom. )
Consequence
MYO1B
NM_001130158.3 missense
NM_001130158.3 missense
Scores
11
6
1
Clinical Significance
Conservation
PhyloP100: 7.78
Genes affected
MYO1B (HGNC:7596): (myosin IB) Enables ATP binding activity; actin filament binding activity; and microfilament motor activity. Involved in actin filament organization and post-Golgi vesicle-mediated transport. Located in several cellular components, including actin filament; endosome; and perinuclear region of cytoplasm. Colocalizes with trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MYO1B
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.958
BS2
?
High AC in GnomAd at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1B | NM_001130158.3 | c.2087T>C | p.Leu696Ser | missense_variant | 20/31 | ENST00000392318.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1B | ENST00000392318.8 | c.2087T>C | p.Leu696Ser | missense_variant | 20/31 | 1 | NM_001130158.3 | P1 | |
MYO1B | ENST00000304164.8 | c.2087T>C | p.Leu696Ser | missense_variant | 20/31 | 1 | P1 | ||
MYO1B | ENST00000339514.8 | c.2087T>C | p.Leu696Ser | missense_variant | 20/29 | 1 | |||
MYO1B | ENST00000392316.5 | c.2087T>C | p.Leu696Ser | missense_variant | 19/29 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
20
AN:
152178
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000112 AC: 28AN: 251100Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135752
GnomAD3 exomes
AF:
AC:
28
AN:
251100
Hom.:
AF XY:
AC XY:
11
AN XY:
135752
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000278 AC: 406AN: 1461156Hom.: 1 Cov.: 30 AF XY: 0.000267 AC XY: 194AN XY: 726942
GnomAD4 exome
AF:
AC:
406
AN:
1461156
Hom.:
Cov.:
30
AF XY:
AC XY:
194
AN XY:
726942
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74340
GnomAD4 genome
?
AF:
AC:
20
AN:
152178
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
74340
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
8
ExAC
?
AF:
AC:
15
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
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 | Apr 28, 2023 | The c.2087T>C (p.L696S) alteration is located in exon 20 (coding exon 19) of the MYO1B gene. This alteration results from a T to C substitution at nucleotide position 2087, causing the leucine (L) at amino acid position 696 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;.
Vest4
MVP
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at