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GeneBe

1-112659765-G-A

Variant summary

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

The NM_006135.3(CAPZA1):c.571G>A(p.Val191Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,612,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.83
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CAPZA1NM_006135.3 linkuse as main transcriptc.571G>A p.Val191Met missense_variant 7/10 ENST00000263168.4
CAPZA1XM_017002424.3 linkuse as main transcriptc.571G>A p.Val191Met missense_variant 7/10
CAPZA1XM_011542225.4 linkuse as main transcriptc.571G>A p.Val191Met missense_variant 7/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CAPZA1ENST00000263168.4 linkuse as main transcriptc.571G>A p.Val191Met missense_variant 7/101 NM_006135.3 P1
CAPZA1ENST00000466066.1 linkuse as main transcriptn.437G>A non_coding_transcript_exon_variant 1/42
CAPZA1ENST00000476936.5 linkuse as main transcriptn.326G>A non_coding_transcript_exon_variant 5/83
CAPZA1ENST00000498626.1 linkuse as main transcriptn.624G>A non_coding_transcript_exon_variant 8/95

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152012
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251018
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135692
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000685
AC:
10
AN:
1460746
Hom.:
0
Cov.:
30
AF XY:
0.00000688
AC XY:
5
AN XY:
726730
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152130
Hom.:
0
Cov.:
30
AF XY:
0.0000269
AC XY:
2
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 14, 2023The c.571G>A (p.V191M) alteration is located in exon 7 (coding exon 7) of the CAPZA1 gene. This alteration results from a G to A substitution at nucleotide position 571, causing the valine (V) at amino acid position 191 to be replaced by a methionine (M). 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
Benign
0.27
BayesDel_addAF
Benign
0.0081
T
BayesDel_noAF
Benign
-0.23
Cadd
Uncertain
25
Dann
Uncertain
0.99
DEOGEN2
Benign
0.053
T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.0026
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.98
N
REVEL
Benign
0.15
Sift
Benign
0.15
T
Sift4G
Benign
0.25
T
Polyphen
0.98
D
Vest4
0.48
MutPred
0.48
Loss of catalytic residue at V191 (P = 0.0331);
MVP
0.42
MPC
0.34
ClinPred
0.59
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.33
gMVP
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs765415236; hg19: chr1-113202387; API