chr14-58200274-C-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_018477.3(ACTR10):āc.57C>Gā(p.Asp19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,512,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000022 ( 0 hom. )
Consequence
ACTR10
NM_018477.3 missense
NM_018477.3 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 1.29
Genes affected
ACTR10 (HGNC:17372): (actin related protein 10) Predicted to be involved in retrograde axonal transport of mitochondrion. Predicted to be located in cytosol; extracellular region; and secretory granule. Predicted to be part of dynactin complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.971
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTR10 | NM_018477.3 | c.57C>G | p.Asp19Glu | missense_variant | 1/13 | ENST00000254286.9 | NP_060947.1 | |
ACTR10 | XM_011536960.2 | c.57C>G | p.Asp19Glu | missense_variant | 1/13 | XP_011535262.1 | ||
ACTR10 | XM_011536961.2 | c.57C>G | p.Asp19Glu | missense_variant | 1/12 | XP_011535263.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTR10 | ENST00000254286.9 | c.57C>G | p.Asp19Glu | missense_variant | 1/13 | 1 | NM_018477.3 | ENSP00000254286 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151710Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000121 AC: 2AN: 165246Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 92860
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GnomAD4 exome AF: 0.00000221 AC: 3AN: 1360506Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 676568
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GnomAD4 genome AF: 0.0000132 AC: 2AN: 151710Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74058
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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 | Jul 14, 2022 | The c.57C>G (p.D19E) alteration is located in exon 1 (coding exon 1) of the ACTR10 gene. This alteration results from a C to G substitution at nucleotide position 57, causing the aspartic acid (D) at amino acid position 19 to be replaced by a glutamic acid (E). 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
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N
REVEL
Pathogenic
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of sheet (P = 0.1158);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at