chr14-58223622-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_018477.3(ACTR10):​c.635C>T​(p.Ala212Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,609,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

ACTR10
NM_018477.3 missense, splice_region

Scores

2
17
Splicing: ADA: 0.0002272
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.91
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 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=0.14898041).
BP6
Variant 14-58223622-C-T is Benign according to our data. Variant chr14-58223622-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3142283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACTR10NM_018477.3 linkuse as main transcriptc.635C>T p.Ala212Val missense_variant, splice_region_variant 9/13 ENST00000254286.9 NP_060947.1
ACTR10XM_011536960.2 linkuse as main transcriptc.656C>T p.Ala219Val missense_variant 9/13 XP_011535262.1
ACTR10XM_047431587.1 linkuse as main transcriptc.62C>T p.Ala21Val missense_variant 4/8 XP_047287543.1
ACTR10XM_011536961.2 linkuse as main transcriptc.599C>T p.Ala200Val missense_variant, splice_region_variant 8/12 XP_011535263.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACTR10ENST00000254286.9 linkuse as main transcriptc.635C>T p.Ala212Val missense_variant, splice_region_variant 9/131 NM_018477.3 ENSP00000254286 P1

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151806
Hom.:
0
Cov.:
32
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000163
AC:
4
AN:
245230
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132748
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000554
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000270
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000535
AC:
78
AN:
1457298
Hom.:
0
Cov.:
30
AF XY:
0.0000566
AC XY:
41
AN XY:
724706
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000657
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151806
Hom.:
0
Cov.:
32
AF XY:
0.0000405
AC XY:
3
AN XY:
74094
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000474
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 27, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
16
DANN
Benign
0.80
DEOGEN2
Benign
0.28
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
-2.1
N
MutationTaster
Benign
0.76
N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
3.2
N
REVEL
Uncertain
0.30
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.18
MVP
0.85
MPC
0.29
ClinPred
0.055
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.022
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00023
dbscSNV1_RF
Benign
0.080
SpliceAI score (max)
0.010
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: rs146482278; hg19: chr14-58690340; API