Variant chr14-58219703-C-T details in Genebe, Genetics Data Aggregator

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

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]

ACTR10 links:

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

ARMH4 links:

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
ACTR10	NM_018477.3 linkuse as main transcript	c.608C>T	p.Pro203Leu	missense_variant	8/13	ENST00000254286.9
ACTR10	XM_011536960.2 linkuse as main transcript	c.608C>T	p.Pro203Leu	missense_variant	8/13
ACTR10	XM_047431587.1 linkuse as main transcript	c.14C>T	p.Pro5Leu	missense_variant	3/8
ACTR10	XM_011536961.2 linkuse as main transcript	c.599-3919C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR10	ENST00000254286.9 linkuse as main transcript	c.608C>T	p.Pro203Leu	missense_variant	8/13	1	NM_018477.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152048

Hom.:

Cov.:

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:

AN:

192666

Hom.:

AF XY:

0.000226

AC XY:

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.:

Cov.:

AF XY:

0.000112

AC XY:

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:

AN:

152048

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

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.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000181

AC:

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

Nov 12, 2021

The 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

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.052

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.54

Sift

Uncertain

0.011

Sift4G

Benign

0.076

Polyphen

0.60

Vest4

0.53

MVP

0.95

MPC

0.51

ClinPred

0.10

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over