chr14-58215246-C-A

Variant summary

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

The NM_018477.3(ACTR10):​c.560C>A​(p.Thr187Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000497 in 1,610,684 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACTR10
NM_018477.3 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.13
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]

Genome browser will be placed here

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 linkc.560C>A p.Thr187Lys missense_variant 7/13 ENST00000254286.9 NP_060947.1 Q9NZ32
ACTR10XM_011536960.2 linkc.560C>A p.Thr187Lys missense_variant 7/13 XP_011535262.1
ACTR10XM_011536961.2 linkc.560C>A p.Thr187Lys missense_variant 7/12 XP_011535263.1
ACTR10XM_047431587.1 linkc.-35C>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 linkc.560C>A p.Thr187Lys missense_variant 7/131 NM_018477.3 ENSP00000254286.4 Q9NZ32
ACTR10ENST00000554402.6 linkn.557C>A non_coding_transcript_exon_variant 7/141 ENSP00000477173.1 V9GYX7

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151876
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
249238
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134726
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000329
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458808
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
725654
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000506
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151876
Hom.:
0
Cov.:
30
AF XY:
0.0000674
AC XY:
5
AN XY:
74136
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642
ExAC
AF:
0.0000165
AC:
2

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 GeneticsApr 24, 2024The c.560C>A (p.T187K) 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 560, causing the threonine (T) at amino acid position 187 to be replaced by a lysine (K). 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
0.23
BayesDel_addAF
Benign
-0.062
T
BayesDel_noAF
Pathogenic
0.14
CADD
Benign
22
DANN
Benign
0.87
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.58
D
MetaSVM
Uncertain
0.65
D
MutationAssessor
Uncertain
2.9
M
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-1.5
N
REVEL
Pathogenic
0.67
Sift
Benign
0.30
T
Sift4G
Benign
0.70
T
Polyphen
0.17
B
Vest4
0.79
MutPred
0.53
Gain of solvent accessibility (P = 0.0086);
MVP
0.94
MPC
0.55
ClinPred
0.22
T
GERP RS
4.6
Varity_R
0.12
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs764509830; hg19: chr14-58681964; API