1-112647213-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006135.3(CAPZA1):​c.43C>A​(p.Arg15Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000736 in 1,358,364 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R15C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

6
4
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.77
Variant links:
Genes affected
CAPZA1 (HGNC:1488): (capping actin protein of muscle Z-line subunit alpha 1) CAPZA1 is a member of the F-actin capping protein alpha subunit family. This gene encodes the alpha subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAPZA1NM_006135.3 linkc.43C>A p.Arg15Ser missense_variant Exon 2 of 10 ENST00000263168.4 NP_006126.1 P52907
CAPZA1XM_017002424.3 linkc.43C>A p.Arg15Ser missense_variant Exon 2 of 10 XP_016857913.1
CAPZA1XM_011542225.4 linkc.43C>A p.Arg15Ser missense_variant Exon 2 of 9 XP_011540527.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAPZA1ENST00000263168.4 linkc.43C>A p.Arg15Ser missense_variant Exon 2 of 10 1 NM_006135.3 ENSP00000263168.3 P52907
CAPZA1ENST00000476936.5 linkn.69C>A non_coding_transcript_exon_variant Exon 2 of 8 3
CAPZA1ENST00000485542.5 linkn.83C>A non_coding_transcript_exon_variant Exon 2 of 3 2
CAPZA1ENST00000498626.1 linkn.96C>A non_coding_transcript_exon_variant Exon 3 of 9 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.36e-7
AC:
1
AN:
1358364
Hom.:
0
Cov.:
25
AF XY:
0.00
AC XY:
0
AN XY:
673926
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:
9.54e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.39
D
BayesDel_noAF
Pathogenic
0.32
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.32
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0037
T
MetaRNN
Pathogenic
0.77
D
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.7
L
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.8
D
REVEL
Benign
0.27
Sift
Uncertain
0.012
D
Sift4G
Benign
0.19
T
Polyphen
0.076
B
Vest4
0.81
MutPred
0.55
Gain of ubiquitination at K19 (P = 0.0483);
MVP
0.77
MPC
0.30
ClinPred
0.97
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.64
gMVP
0.74

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: chr1-113189835; API