chr2-97658459-C-T

Variant summary

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

The NM_005735.4(ACTR1B):​c.625G>A​(p.Ala209Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A209P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACTR1B
NM_005735.4 missense

Scores

8
10
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17
Variant links:
Genes affected
ACTR1B (HGNC:168): (actin related protein 1B) This gene encodes a 42.3 kD subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein and is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit, like ACTR1A, is an actin-related protein. These two proteins, which are of equal length and share 90% amino acid identity, are present in a constant ratio of approximately 1:15 in the dynactin complex. [provided by RefSeq, Aug 2008]

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 rank MANE Protein UniProt
ACTR1BNM_005735.4 linkc.625G>A p.Ala209Thr missense_variant Exon 6 of 11 ENST00000289228.7 NP_005726.1 P42025
ACTR1BXM_017003116.2 linkc.493G>A p.Ala165Thr missense_variant Exon 6 of 11 XP_016858605.1
ACTR1BXM_005263854.6 linkc.403G>A p.Ala135Thr missense_variant Exon 5 of 10 XP_005263911.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACTR1BENST00000289228.7 linkc.625G>A p.Ala209Thr missense_variant Exon 6 of 11 1 NM_005735.4 ENSP00000289228.5 P42025
ACTR1BENST00000451664.1 linkn.886G>A non_coding_transcript_exon_variant Exon 5 of 7 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251312
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
6.84e-7
AC:
1
AN:
1461868
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
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
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Pathogenic
0.24
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.69
D
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D
M_CAP
Uncertain
0.14
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Pathogenic
0.87
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.1
D
REVEL
Pathogenic
0.75
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.019
D
Polyphen
0.069
B
Vest4
0.53
MutPred
0.71
Loss of helix (P = 0.0558);
MVP
0.95
MPC
0.63
ClinPred
0.96
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.59
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs780715402; hg19: chr2-98274922; API