Genetic Variant CAPZA3:p.Thr265Ala (chr12-18739061-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_033328.3(CAPZA3):c.793A>G(p.Thr265Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000374 in 1,612,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

CAPZA3
NM_033328.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60

Publications

2 publications found

Variant links:

Genes affected

CAPZA3 (HGNC:24205): (capping actin protein of muscle Z-line subunit alpha 3) This gene encodes an actin capping protein, one of the F-actin capping protein alpha subunit family. The encoded protein is predominantly localized to the neck region of ejaculated sperm, other immunohistochemical signals were found in the tail and postacrosomal regions. The encoded protein may also form heterodimers of alpha and beta subunits. This protein may be important in determining sperm architecture and male fertility. [provided by RefSeq, Jul 2008]

CAPZA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPZA3	NM_033328.3 link	c.793A>G	p.Thr265Ala	missense_variant	Exon 1 of 1	ENST00000317658.5	NP_201585.1	Q96KX2A0A140VKF6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPZA3	ENST00000317658.5 link	c.793A>G	p.Thr265Ala	missense_variant	Exon 1 of 1	6	NM_033328.3	ENSP00000326238.3		Q96KX2

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000269

AC:

AN:

248620

AF XY:

0.000282

show subpopulations

Gnomad AFR exome

AF:

0.0000627

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000577

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000377

AC:

551

AN:

1460100

Hom.:

Cov.:

AF XY:

0.000373

AC XY:

271

AN XY:

726416

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000579

AC:

AN:

51848

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000475

AC:

528

AN:

1111882

Other (OTH)

AF:

0.000199

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000342

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41366

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000557

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000655

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 09, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.793A>G (p.T265A) alteration is located in exon 1 (coding exon 1) of the CAPZA3 gene. This alteration results from a A to G substitution at nucleotide position 793, causing the threonine (T) at amino acid position 265 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

Benign

0.28

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.60

M_CAP

Benign

0.0084

MetaRNN

Uncertain

0.64

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.9

PhyloP100

5.6

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.23

Sift

Benign

0.10

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.66

MVP

0.70

MPC

0.13

ClinPred

0.15

GERP RS

4.6

Varity_R

0.30

gMVP

0.34

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

12-18739061-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over