chr14-58223811-A-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_018477.3(ACTR10):āc.743A>Gā(p.Tyr248Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,110 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: not found (cov: 32)
Exomes š: 0.0000082 ( 0 hom. )
Consequence
ACTR10
NM_018477.3 missense
NM_018477.3 missense
Scores
13
5
1
Clinical Significance
Conservation
PhyloP100: 8.79
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, 0.959
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ACTR10 | NM_018477.3 | c.743A>G | p.Tyr248Cys | missense_variant | 10/13 | ENST00000254286.9 | NP_060947.1 | |
ACTR10 | XM_011536960.2 | c.764A>G | p.Tyr255Cys | missense_variant | 10/13 | XP_011535262.1 | ||
ACTR10 | XM_011536961.2 | c.707A>G | p.Tyr236Cys | missense_variant | 9/12 | XP_011535263.1 | ||
ACTR10 | XM_047431587.1 | c.170A>G | p.Tyr57Cys | missense_variant | 5/8 | XP_047287543.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ACTR10 | ENST00000254286.9 | c.743A>G | p.Tyr248Cys | missense_variant | 10/13 | 1 | NM_018477.3 | ENSP00000254286 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251230Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135760
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461110Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 726898
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GnomAD4 genome Cov.: 32
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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 | Apr 09, 2024 | The c.743A>G (p.Y248C) alteration is located in exon 10 (coding exon 10) of the ACTR10 gene. This alteration results from a A to G substitution at nucleotide position 743, causing the tyrosine (Y) at amino acid position 248 to be replaced by a cysteine (C). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of loop (P = 0.0502);
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