Variant 1-112653620-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006135.3(CAPZA1):c.178G>A(p.Asp60Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,445,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CAPZA1
NM_006135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.89

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA1	NM_006135.3 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	4/10	ENST00000263168.4	NP_006126.1	P52907
CAPZA1	XM_017002424.3 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	4/10		XP_016857913.1
CAPZA1	XM_011542225.4 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	4/9		XP_011540527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPZA1	ENST00000263168.4 linkuse as main transcript	c.178G>A	p.Asp60Asn	missense_variant	4/10	1	NM_006135.3	ENSP00000263168.3	P52907
CAPZA1	ENST00000498626.1 linkuse as main transcript	n.231G>A		non_coding_transcript_exon_variant	5/9	5
CAPZA1	ENST00000476936.5 linkuse as main transcript	n.181+4151G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000837

AC:

AN:

239056

Hom.:

AF XY:

0.00000773

AC XY:

AN XY:

129448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000629

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1445858

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

719068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000938

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000882

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

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

Mar 21, 2022

The c.178G>A (p.D60N) alteration is located in exon 4 (coding exon 4) of the CAPZA1 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the aspartic acid (D) at amino acid position 60 to be replaced by an asparagine (N). 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

0.92

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0092

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.4

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.44

Sift

Uncertain

0.027

Sift4G

Benign

0.10

Polyphen

0.96

Vest4

0.72

MutPred

0.41

Loss of phosphorylation at T63 (P = 0.2307);

MVP

0.46

MPC

0.35

ClinPred

0.96

GERP RS

4.8

Varity_R

0.76

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.25

Position offset: -22

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