9-108862402-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006687.4(ACTL7A):​c.80C>T​(p.Ala27Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. A27D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ACTL7A
NM_006687.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.848
Variant links:
Genes affected
ACTL7A (HGNC:161): (actin like 7A) The protein encoded by this gene is a member of a family of actin-related proteins (ARPs) which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene (ACTL7A), and related gene, ACTL7B, are intronless, and are located approximately 4 kb apart in a head-to-head orientation within the familial dysautonomia candidate region on 9q31. Based on mutational analysis of the ACTL7A gene in patients with this disorder, it was concluded that it is unlikely to be involved in the pathogenesis of dysautonomia. The ACTL7A gene is expressed in a wide variety of adult tissues, however, its exact function is not known. [provided by RefSeq, Jul 2008]

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=0.04055214).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACTL7ANM_006687.4 linkc.80C>T p.Ala27Val missense_variant Exon 1 of 1 ENST00000333999.5 NP_006678.1 Q9Y615A0A140VK03

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACTL7AENST00000333999.5 linkc.80C>T p.Ala27Val missense_variant Exon 1 of 1 6 NM_006687.4 ENSP00000334300.3 Q9Y615

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461770
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727184
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:
0.00000450
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
Benign
0.068
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
0.93
DANN
Benign
0.89
DEOGEN2
Benign
0.013
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.041
T
MetaSVM
Uncertain
-0.25
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.29
Sift
Benign
0.61
T
Sift4G
Benign
0.19
T
Polyphen
0.0
B
Vest4
0.077
MutPred
0.33
Gain of sheet (P = 0.0016);
MVP
0.55
MPC
0.077
ClinPred
0.035
T
GERP RS
-3.1
Varity_R
0.028
gMVP
0.14

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: chr9-111624682; COSMIC: COSV61776289; API