chr14-58223813-C-G
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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):āc.745C>Gā(p.Pro249Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,072 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 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000096 ( 0 hom. )
Consequence
ACTR10
NM_018477.3 missense
NM_018477.3 missense
Scores
8
9
2
Clinical Significance
Conservation
PhyloP100: 7.46
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, 0.884
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTR10 | NM_018477.3 | c.745C>G | p.Pro249Ala | missense_variant | 10/13 | ENST00000254286.9 | NP_060947.1 | |
ACTR10 | XM_011536960.2 | c.766C>G | p.Pro256Ala | missense_variant | 10/13 | XP_011535262.1 | ||
ACTR10 | XM_011536961.2 | c.709C>G | p.Pro237Ala | missense_variant | 9/12 | XP_011535263.1 | ||
ACTR10 | XM_047431587.1 | c.172C>G | p.Pro58Ala | missense_variant | 5/8 | XP_047287543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTR10 | ENST00000254286.9 | c.745C>G | p.Pro249Ala | missense_variant | 10/13 | 1 | NM_018477.3 | ENSP00000254286 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461046Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726882
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152026Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74230
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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 17, 2023 | The c.745C>G (p.P249A) alteration is located in exon 10 (coding exon 10) of the ACTR10 gene. This alteration results from a C to G substitution at nucleotide position 745, causing the proline (P) at amino acid position 249 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Benign
T
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of disorder (P = 0.0507);
MVP
MPC
ClinPred
D
GERP RS
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