14-58219703-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_018477.3(ACTR10):c.608C>T(p.Pro203Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000112 in 1,517,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
ACTR10
NM_018477.3 missense
NM_018477.3 missense
Scores
1
13
5
Clinical Significance
Conservation
PhyloP100: 6.11
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_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05237779).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTR10 | NM_018477.3 | c.608C>T | p.Pro203Leu | missense_variant | 8/13 | ENST00000254286.9 | NP_060947.1 | |
ACTR10 | XM_011536960.2 | c.608C>T | p.Pro203Leu | missense_variant | 8/13 | XP_011535262.1 | ||
ACTR10 | XM_047431587.1 | c.14C>T | p.Pro5Leu | missense_variant | 3/8 | XP_047287543.1 | ||
ACTR10 | XM_011536961.2 | c.599-3919C>T | intron_variant | XP_011535263.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTR10 | ENST00000254286.9 | c.608C>T | p.Pro203Leu | missense_variant | 8/13 | 1 | NM_018477.3 | ENSP00000254286 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152048Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000197 AC: 38AN: 192666Hom.: 0 AF XY: 0.000226 AC XY: 24AN XY: 106228
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GnomAD4 exome AF: 0.000108 AC: 148AN: 1365850Hom.: 0 Cov.: 26 AF XY: 0.000112 AC XY: 76AN XY: 678116
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GnomAD4 genome AF: 0.000145 AC: 22AN: 152048Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74246
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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 | Nov 12, 2021 | The c.608C>T (p.P203L) alteration is located in exon 8 (coding exon 8) of the ACTR10 gene. This alteration results from a C to T substitution at nucleotide position 608, causing the proline (P) at amino acid position 203 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
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