Variant 1-112654609-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006135.3(CAPZA1):c.364G>A(p.Glu122Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 1 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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]

CAPZA1 links:

CAPZA1 (HGNC:):

CAPZA1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16281325).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA1	NM_006135.3 linkuse as main transcript	c.364G>A	p.Glu122Lys	missense_variant	5/10	ENST00000263168.4	NP_006126.1	P52907
CAPZA1	XM_017002424.3 linkuse as main transcript	c.364G>A	p.Glu122Lys	missense_variant	5/10		XP_016857913.1
CAPZA1	XM_011542225.4 linkuse as main transcript	c.364G>A	p.Glu122Lys	missense_variant	5/9		XP_011540527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPZA1	ENST00000263168.4 linkuse as main transcript	c.364G>A	p.Glu122Lys	missense_variant	5/10	1	NM_006135.3	ENSP00000263168.3	P52907
CAPZA1	ENST00000498626.1 linkuse as main transcript	n.417G>A		non_coding_transcript_exon_variant	6/9	5
CAPZA1	ENST00000476936.5 linkuse as main transcript	n.182-4413G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250958

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135798

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:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.364G>A (p.E122K) alteration is located in exon 5 (coding exon 5) of the CAPZA1 gene. This alteration results from a G to A substitution at nucleotide position 364, causing the glutamic acid (E) at amino acid position 122 to be replaced by a lysine (K). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.083

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0029

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.26

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.53

REVEL

Benign

0.053

Sift

Benign

0.72

Sift4G

Benign

0.84

Polyphen

0.033

Vest4

0.31

MutPred

0.52

Gain of MoRF binding (P = 0.0048);

MVP

0.28

MPC

0.29

ClinPred

0.41

GERP RS

4.6

Varity_R

0.21

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over