chr14-58223652-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_018477.3(ACTR10):c.665G>A(p.Arg222Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,472 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
ACTR10
NM_018477.3 missense
NM_018477.3 missense
Scores
6
11
2
Clinical Significance
Conservation
PhyloP100: 9.05
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.932
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTR10 | NM_018477.3 | c.665G>A | p.Arg222Gln | missense_variant | 9/13 | ENST00000254286.9 | NP_060947.1 | |
ACTR10 | XM_011536960.2 | c.686G>A | p.Arg229Gln | missense_variant | 9/13 | XP_011535262.1 | ||
ACTR10 | XM_011536961.2 | c.629G>A | p.Arg210Gln | missense_variant | 8/12 | XP_011535263.1 | ||
ACTR10 | XM_047431587.1 | c.92G>A | p.Arg31Gln | missense_variant | 4/8 | XP_047287543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTR10 | ENST00000254286.9 | c.665G>A | p.Arg222Gln | missense_variant | 9/13 | 1 | NM_018477.3 | ENSP00000254286 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151518Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249728Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135164
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1460954Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726686
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GnomAD4 genome AF: 0.00000660 AC: 1AN: 151518Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73932
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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 | Oct 13, 2021 | The c.665G>A (p.R222Q) alteration is located in exon 9 (coding exon 9) of the ACTR10 gene. This alteration results from a G to A substitution at nucleotide position 665, causing the arginine (R) at amino acid position 222 to be replaced by a glutamine (Q). 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
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0152);
MVP
MPC
ClinPred
D
GERP RS
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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