1-112647213-C-G

Variant summary

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

The NM_006135.3(CAPZA1):​c.43C>G​(p.Arg15Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000736 in 1,358,366 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 š‘“: 7.4e-7 ( 0 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

8
6
5

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
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAPZA1NM_006135.3 linkc.43C>G p.Arg15Gly missense_variant Exon 2 of 10 ENST00000263168.4 NP_006126.1 P52907
CAPZA1XM_017002424.3 linkc.43C>G p.Arg15Gly missense_variant Exon 2 of 10 XP_016857913.1
CAPZA1XM_011542225.4 linkc.43C>G p.Arg15Gly 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>G p.Arg15Gly missense_variant Exon 2 of 10 1 NM_006135.3 ENSP00000263168.3 P52907
CAPZA1ENST00000476936.5 linkn.69C>G non_coding_transcript_exon_variant Exon 2 of 8 3
CAPZA1ENST00000485542.5 linkn.83C>G non_coding_transcript_exon_variant Exon 2 of 3 2
CAPZA1ENST00000498626.1 linkn.96C>G non_coding_transcript_exon_variant Exon 3 of 9 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.36e-7
AC:
1
AN:
1358366
Hom.:
0
Cov.:
25
AF XY:
0.00000148
AC XY:
1
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
0.56
BayesDel_addAF
Pathogenic
0.42
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.28
T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.0050
T
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.66
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.031
D
Polyphen
0.076
B
Vest4
0.84
MutPred
0.59
Gain of ubiquitination at K19 (P = 0.0505);
MVP
0.77
MPC
0.55
ClinPred
0.98
D
GERP RS
5.7
Varity_R
0.80
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.54
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.54
Position offset: 1

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