rs545492504

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004998.4(MYO1E):​c.3236A>T​(p.Asp1079Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

MYO1E
NM_004998.4 missense

Scores

2
9
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.00
Variant links:
Genes affected
MYO1E (HGNC:7599): (myosin IE) This gene encodes a member of the nonmuscle class I myosins which are a subgroup of the unconventional myosin protein family. The unconventional myosin proteins function as actin-based molecular motors. Class I myosins are characterized by a head (motor) domain, a regulatory domain and a either a short or long tail domain. Among the class I myosins, this protein is distinguished by a long tail domain that is involved in crosslinking actin filaments. This protein localizes to the cytoplasm and may be involved in intracellular movement and membrane trafficking. Mutations in this gene are the cause of focal segmental glomerulosclerosis-6. This gene has been referred to as myosin IC in the literature but is distinct from the myosin IC gene located on chromosome 17. [provided by RefSeq, Jan 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYO1ENM_004998.4 linkc.3236A>T p.Asp1079Val missense_variant Exon 27 of 28 ENST00000288235.9 NP_004989.2 Q12965Q4KMR3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYO1EENST00000288235.9 linkc.3236A>T p.Asp1079Val missense_variant Exon 27 of 28 1 NM_004998.4 ENSP00000288235.4 Q12965
MYO1EENST00000559412.1 linkc.129+80A>T intron_variant Intron 2 of 2 3 ENSP00000453936.1 H0YNB0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251460
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.32
T
Eigen
Benign
0.19
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.66
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.13
N
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Uncertain
0.30
Sift
Benign
0.054
T
Sift4G
Benign
0.33
T
Polyphen
0.44
B
Vest4
0.73
MutPred
0.54
Loss of ubiquitination at K1082 (P = 0.0837);
MVP
0.77
MPC
0.57
ClinPred
0.93
D
GERP RS
5.8
Varity_R
0.50
gMVP
0.61

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: rs545492504; hg19: chr15-59430411; API