Variant 1-112619878-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_006135.3(CAPZA1):c.34G>A(p.Glu12Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0037 in 1,611,892 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 24 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 6.19

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012323827).

BP6

Variant 1-112619878-G-A is Benign according to our data. Variant chr1-112619878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206064.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-112619878-G-A is described in Lovd as [Benign]. Variant chr1-112619878-G-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 343 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA1	NM_006135.3 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	1/10	ENST00000263168.4	NP_006126.1	P52907
CAPZA1	XM_017002424.3 linkuse as main transcript	c.34G>A	p.Glu12Lys	missense_variant	1/10		XP_016857913.1
CAPZA1	XM_011542225.4 linkuse as main transcript	c.34G>A	p.Glu12Lys	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.34G>A	p.Glu12Lys	missense_variant	1/10	1	NM_006135.3	ENSP00000263168.3		P52907

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00340

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00193

AC:

472

AN:

244770

Hom.:

AF XY:

0.00203

AC XY:

270

AN XY:

132836

show subpopulations

Gnomad AFR exome

AF:

0.000779

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.000303

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000938

Gnomad FIN exome

AF:

0.000434

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00385

AC:

5619

AN:

1459546

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

2731

AN XY:

725964

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000863

Gnomad4 FIN exome

AF:

0.000433

Gnomad4 NFE exome

AF:

0.00474

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00225

AC:

343

AN:

152346

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.00340

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00244

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00182

AC:

221

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.038

BayesDel_noAF

Pathogenic

0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0050

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.26

Sift

Benign

0.073

Sift4G

Benign

0.11

Polyphen

0.0010

Vest4

0.62

MVP

0.85

MPC

0.32

ClinPred

0.030

GERP RS

6.2

Varity_R

0.59

gMVP

0.71

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