chr2-191392172-T-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_001130158.3(MYO1B):c.2047T>A(p.Ser683Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000814 in 1,607,482 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00083 ( 2 hom. )
Consequence
MYO1B
NM_001130158.3 missense
NM_001130158.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 4.65
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 Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MYO1B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.033437252).
BS2
?
High AC in GnomAd at 103 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO1B | NM_001130158.3 | c.2047T>A | p.Ser683Thr | missense_variant | 19/31 | ENST00000392318.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO1B | ENST00000392318.8 | c.2047T>A | p.Ser683Thr | missense_variant | 19/31 | 1 | NM_001130158.3 | P1 | |
MYO1B | ENST00000304164.8 | c.2047T>A | p.Ser683Thr | missense_variant | 19/31 | 1 | P1 | ||
MYO1B | ENST00000339514.8 | c.2047T>A | p.Ser683Thr | missense_variant | 19/29 | 1 | |||
MYO1B | ENST00000392316.5 | c.2047T>A | p.Ser683Thr | missense_variant | 18/29 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000677 AC: 103AN: 152220Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
103
AN:
152220
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: 0.000661 AC: 166AN: 251240Hom.: 0 AF XY: 0.000677 AC XY: 92AN XY: 135860
GnomAD3 exomes
AF:
AC:
166
AN:
251240
Hom.:
AF XY:
AC XY:
92
AN XY:
135860
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: 0.000829 AC: 1206AN: 1455144Hom.: 2 Cov.: 30 AF XY: 0.000827 AC XY: 598AN XY: 723384
GnomAD4 exome
AF:
AC:
1206
AN:
1455144
Hom.:
Cov.:
30
AF XY:
AC XY:
598
AN XY:
723384
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: 0.000676 AC: 103AN: 152338Hom.: 0 Cov.: 32 AF XY: 0.000685 AC XY: 51AN XY: 74496
GnomAD4 genome
?
AF:
AC:
103
AN:
152338
Hom.:
Cov.:
32
AF XY:
AC XY:
51
AN XY:
74496
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:
6
ALSPAC
AF:
AC:
3
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
8
ExAC
?
AF:
AC:
73
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 | Oct 22, 2021 | The c.2047T>A (p.S683T) alteration is located in exon 19 (coding exon 18) of the MYO1B gene. This alteration results from a T to A substitution at nucleotide position 2047, causing the serine (S) at amino acid position 683 to be replaced by a threonine (T). 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
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;B;B;.
Vest4
MVP
MPC
0.42
ClinPred
T
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