chr14-58219703-C-T

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

Scores

1
13
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11
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 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
ACTR10NM_018477.3 linkuse as main transcriptc.608C>T p.Pro203Leu missense_variant 8/13 ENST00000254286.9 NP_060947.1
ACTR10XM_011536960.2 linkuse as main transcriptc.608C>T p.Pro203Leu missense_variant 8/13 XP_011535262.1
ACTR10XM_047431587.1 linkuse as main transcriptc.14C>T p.Pro5Leu missense_variant 3/8 XP_047287543.1
ACTR10XM_011536961.2 linkuse as main transcriptc.599-3919C>T intron_variant XP_011535263.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACTR10ENST00000254286.9 linkuse as main transcriptc.608C>T p.Pro203Leu missense_variant 8/131 NM_018477.3 ENSP00000254286 P1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152048
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00259
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000197
AC:
38
AN:
192666
Hom.:
0
AF XY:
0.000226
AC XY:
24
AN XY:
106228
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00352
Gnomad EAS exome
AF:
0.0000799
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000666
Gnomad OTH exome
AF:
0.000450
GnomAD4 exome
AF:
0.000108
AC:
148
AN:
1365850
Hom.:
0
Cov.:
26
AF XY:
0.000112
AC XY:
76
AN XY:
678116
show subpopulations
Gnomad4 AFR exome
AF:
0.0000350
Gnomad4 AMR exome
AF:
0.0000311
Gnomad4 ASJ exome
AF:
0.00301
Gnomad4 EAS exome
AF:
0.0000286
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000536
Gnomad4 OTH exome
AF:
0.000269
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152048
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74246
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00259
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000533
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000582
AC:
5
ExAC
AF:
0.000181
AC:
22

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 GeneticsNov 12, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.052
T
MetaSVM
Uncertain
0.41
D
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.54
Sift
Uncertain
0.011
D
Sift4G
Benign
0.076
T
Polyphen
0.60
P
Vest4
0.53
MVP
0.95
MPC
0.51
ClinPred
0.10
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.14
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs370351893; hg19: chr14-58686421; API