12-100218581-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022496.5(ACTR6):​c.917C>T​(p.Pro306Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ACTR6
NM_022496.5 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.27
Variant links:
Genes affected
ACTR6 (HGNC:24025): (actin related protein 6) Predicted to enable nucleosome binding activity. Predicted to be involved in histone exchange. Predicted to be located in nucleus. Predicted to be part of Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]
DEPDC4 (HGNC:22952): (DEP domain containing 4) Predicted to be involved in intracellular signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.851

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ACTR6NM_022496.5 linkc.917C>T p.Pro306Leu missense_variant Exon 9 of 11 ENST00000188312.7 NP_071941.1 Q9GZN1-1
ACTR6NR_048568.2 linkn.1095C>T non_coding_transcript_exon_variant Exon 9 of 11
ACTR6NR_048569.2 linkn.967C>T non_coding_transcript_exon_variant Exon 9 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ACTR6ENST00000188312.7 linkc.917C>T p.Pro306Leu missense_variant Exon 9 of 11 1 NM_022496.5 ENSP00000188312.2 Q9GZN1-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
27
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.917C>T (p.P306L) alteration is located in exon 9 (coding exon 9) of the ACTR6 gene. This alteration results from a C to T substitution at nucleotide position 917, causing the proline (P) at amino acid position 306 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
Pathogenic
0.64
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.87
D;D;.;D
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.91
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.92
D;D;T;T
M_CAP
Benign
0.058
D
MetaRNN
Pathogenic
0.85
D;D;D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Pathogenic
3.5
M;.;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-9.3
D;D;D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.89
MutPred
0.60
Loss of disorder (P = 0.0278);.;Loss of disorder (P = 0.0278);.;
MVP
0.49
MPC
0.60
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.88
gMVP
0.84

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: chr12-100612359; API