Variant chr1-112669562-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006135.3(CAPZA1):c.677A>G(p.Lys226Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,611,366 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.25

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 -4 ACMG points.

BS2

High AC in GnomAd4 at 47 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA1	NM_006135.3 linkuse as main transcript	c.677A>G	p.Lys226Arg	missense_variant	9/10	ENST00000263168.4	NP_006126.1	P52907
CAPZA1	XM_017002424.3 linkuse as main transcript	c.677A>G	p.Lys226Arg	missense_variant	9/10		XP_016857913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPZA1	ENST00000263168.4 linkuse as main transcript	c.677A>G	p.Lys226Arg	missense_variant	9/10	1	NM_006135.3	ENSP00000263168.3	P52907
CAPZA1	ENST00000466066.1 linkuse as main transcript	n.543A>G		non_coding_transcript_exon_variant	3/4	2
CAPZA1	ENST00000476820.1 linkuse as main transcript	n.246A>G		non_coding_transcript_exon_variant	2/2	3
CAPZA1	ENST00000476936.5 linkuse as main transcript	n.432A>G		non_coding_transcript_exon_variant	7/8	3

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000156

AC:

AN:

250120

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.000186

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:

0.0000462

Gnomad NFE exome

AF:

0.000309

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000408

AC:

596

AN:

1459146

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

295

AN XY:

726046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000527

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000309

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000401

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000771

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

Sep 14, 2022

The c.677A>G (p.K226R) alteration is located in exon 9 (coding exon 9) of the CAPZA1 gene. This alteration results from a A to G substitution at nucleotide position 677, causing the lysine (K) at amino acid position 226 to be replaced by an arginine (R). 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

0.085

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

M_CAP

Benign

0.0041

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.48

Sift

Benign

0.083

Sift4G

Benign

0.28

Polyphen

0.96

Vest4

0.66

MVP

0.51

MPC

0.21

ClinPred

0.20

GERP RS

5.8

Varity_R

0.52

gMVP

0.51

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