17-32654595-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015194.3(MYO1D):​c.2372G>A​(p.Ser791Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MYO1D
NM_015194.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.818
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.073678136).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYO1DNM_015194.3 linkuse as main transcriptc.2372G>A p.Ser791Asn missense_variant 18/22 ENST00000318217.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYO1DENST00000318217.10 linkuse as main transcriptc.2372G>A p.Ser791Asn missense_variant 18/221 NM_015194.3 P1
ENST00000582272.1 linkuse as main transcriptn.141+22116C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460150
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726322
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsJan 04, 2024The c.2372G>A (p.S791N) alteration is located in exon 18 (coding exon 18) of the MYO1D gene. This alteration results from a G to A substitution at nucleotide position 2372, causing the serine (S) at amino acid position 791 to be replaced by an asparagine (N). 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
0.072
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
14
DANN
Benign
0.81
DEOGEN2
Benign
0.042
T;T;T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.40
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.074
T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.65
N;.;.
MutationTaster
Benign
0.56
N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
0.47
N;.;.
REVEL
Benign
0.14
Sift
Benign
0.66
T;.;.
Sift4G
Benign
0.65
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.13
MutPred
0.23
Gain of MoRF binding (P = 0.1048);.;Gain of MoRF binding (P = 0.1048);
MVP
0.75
MPC
0.26
ClinPred
0.11
T
GERP RS
1.1
Varity_R
0.021
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-30981613; API