14-58215244-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018477.3(ACTR10):​c.558C>A​(p.Asp186Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

ACTR10
NM_018477.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.262
Variant links:
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]
ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACTR10NM_018477.3 linkuse as main transcriptc.558C>A p.Asp186Glu missense_variant 7/13 ENST00000254286.9 NP_060947.1
ACTR10XM_011536960.2 linkuse as main transcriptc.558C>A p.Asp186Glu missense_variant 7/13 XP_011535262.1
ACTR10XM_011536961.2 linkuse as main transcriptc.558C>A p.Asp186Glu missense_variant 7/12 XP_011535263.1
ACTR10XM_047431587.1 linkuse as main transcriptc.-37C>A 5_prime_UTR_variant 2/8 XP_047287543.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACTR10ENST00000254286.9 linkuse as main transcriptc.558C>A p.Asp186Glu missense_variant 7/131 NM_018477.3 ENSP00000254286 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
31

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 submitterclinical testingAmbry GeneticsMay 23, 2024The c.558C>A (p.D186E) alteration is located in exon 7 (coding exon 7) of the ACTR10 gene. This alteration results from a C to A substitution at nucleotide position 558, causing the aspartic acid (D) at amino acid position 186 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.28
T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.34
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.072
D
MetaRNN
Uncertain
0.52
D
MetaSVM
Uncertain
-0.22
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.15
N
REVEL
Uncertain
0.49
Sift
Benign
0.29
T
Sift4G
Benign
0.35
T
Polyphen
0.021
B
Vest4
0.73
MutPred
0.53
Gain of disorder (P = 0.0715);
MVP
0.79
MPC
0.29
ClinPred
0.35
T
GERP RS
3.9
Varity_R
0.079
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-58681962; API