rs761570777

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_005735.4(ACTR1B):​c.805G>C​(p.Gly269Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ACTR1B
NM_005735.4 missense

Scores

7
8
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.15
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.989

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACTR1BNM_005735.4 linkc.805G>C p.Gly269Arg missense_variant Exon 8 of 11 ENST00000289228.7 NP_005726.1 P42025
ACTR1BXM_017003116.2 linkc.673G>C p.Gly225Arg missense_variant Exon 8 of 11 XP_016858605.1
ACTR1BXM_005263854.6 linkc.583G>C p.Gly195Arg missense_variant Exon 7 of 10 XP_005263911.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACTR1BENST00000289228.7 linkc.805G>C p.Gly269Arg missense_variant Exon 8 of 11 1 NM_005735.4 ENSP00000289228.5 P42025
ACTR1BENST00000451664.1 linkn.1066G>C non_coding_transcript_exon_variant Exon 7 of 7 5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461774
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
D
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.041
D
MetaRNN
Pathogenic
0.99
D
MetaSVM
Benign
-0.80
T
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Uncertain
0.73
T
PROVEAN
Pathogenic
-7.5
D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.91
P
Vest4
0.93
MutPred
0.82
Gain of solvent accessibility (P = 0.0674);
MVP
0.79
MPC
1.3
ClinPred
1.0
D
GERP RS
3.8
Varity_R
0.85
gMVP
0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-98274526; API