17-32876811-G-A

Variant summary

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

The ENST00000318217.10(MYO1D):​c.62C>T​(p.Ser21Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000937 in 1,525,770 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

MYO1D
ENST00000318217.10 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.00
Variant links:
Genes affected
MYO1D (HGNC:7598): (myosin ID) Enables protein domain specific binding activity. Predicted to be involved in actin filament organization; early endosome to recycling endosome transport; and vesicle transport along actin filament. Located in extracellular exosome. [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 2 ACMG points.

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

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYO1DNM_015194.3 linkuse as main transcriptc.62C>T p.Ser21Phe missense_variant 1/22 ENST00000318217.10 NP_056009.1 O94832Q8N618

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYO1DENST00000318217.10 linkuse as main transcriptc.62C>T p.Ser21Phe missense_variant 1/221 NM_015194.3 ENSP00000324527.5 O94832

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152110
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000100
AC:
138
AN:
1373660
Hom.:
0
Cov.:
30
AF XY:
0.0000958
AC XY:
65
AN XY:
678776
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.000128
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152110
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.0000227

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 submitterclinical testingAmbry GeneticsMar 11, 2024The c.62C>T (p.S21F) alteration is located in exon 1 (coding exon 1) of the MYO1D gene. This alteration results from a C to T substitution at nucleotide position 62, causing the serine (S) at amino acid position 21 to be replaced by a phenylalanine (F). 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
Pathogenic
0.57
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.81
D;D;D
Eigen
Benign
-0.016
Eigen_PC
Benign
0.037
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Pathogenic
0.86
D
MetaRNN
Uncertain
0.55
D;D;D
MetaSVM
Benign
-0.47
T
MutationAssessor
Pathogenic
3.0
M;.;.
MutationTaster
Benign
0.98
D;D;D
PrimateAI
Pathogenic
0.85
D
PROVEAN
Uncertain
-2.9
D;.;.
REVEL
Uncertain
0.44
Sift
Uncertain
0.0020
D;.;.
Sift4G
Uncertain
0.0050
D;D;D
Polyphen
0.0
B;.;.
Vest4
0.34
MutPred
0.60
Loss of phosphorylation at S21 (P = 0.0758);Loss of phosphorylation at S21 (P = 0.0758);Loss of phosphorylation at S21 (P = 0.0758);
MVP
0.75
MPC
0.75
ClinPred
0.93
D
GERP RS
3.7
Varity_R
0.26
gMVP
0.37

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: rs944488520; hg19: chr17-31203829; API