Variant chr1-112619873-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006135.3(CAPZA1):c.29A>C(p.Asp10Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,460,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. D10N) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

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:

ST7L (HGNC:):

ST7L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.29153085).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA1	NM_006135.3 linkuse as main transcript	c.29A>C	p.Asp10Ala	missense_variant	1/10	ENST00000263168.4	NP_006126.1	P52907
CAPZA1	XM_017002424.3 linkuse as main transcript	c.29A>C	p.Asp10Ala	missense_variant	1/10		XP_016857913.1
CAPZA1	XM_011542225.4 linkuse as main transcript	c.29A>C	p.Asp10Ala	missense_variant	1/9		XP_011540527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPZA1	ENST00000263168.4 linkuse as main transcript	c.29A>C	p.Asp10Ala	missense_variant	1/10	1	NM_006135.3	ENSP00000263168.3		P52907

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246196

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133598

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:

0.00000899

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460116

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726274

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:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.00000756

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

Jun 28, 2024

The c.29A>C (p.D10A) alteration is located in exon 1 (coding exon 1) of the CAPZA1 gene. This alteration results from a A to C substitution at nucleotide position 29, causing the aspartic acid (D) at amino acid position 10 to be replaced by an alanine (A). 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

0.59

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.68

M_CAP

Benign

0.0086

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.20

Sift

Benign

0.051

Sift4G

Benign

0.13

Polyphen

0.0070

Vest4

0.54

MutPred

0.25

Loss of ubiquitination at K13 (P = 0.0739);

MVP

0.54

MPC

0.32

ClinPred

1.0

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.61

gMVP

0.66

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