1-112647271-A-G

Position:

chr1-112647271-A-G

Variant summary

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

The NM_006135.3(CAPZA1):c.101A>G(p.Asn34Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000485 in 1,484,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CAPZA1
NM_006135.3 missense, splice_region

Scores

Splicing: ADA: 0.5985

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.83

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:

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=0.34056044).

BS2

High AC in GnomAdExome4 at 68 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPZA1	NM_006135.3 linkuse as main transcript	c.101A>G	p.Asn34Ser	missense_variant, splice_region_variant	2/10	ENST00000263168.4	NP_006126.1	P52907
CAPZA1	XM_017002424.3 linkuse as main transcript	c.101A>G	p.Asn34Ser	missense_variant, splice_region_variant	2/10		XP_016857913.1
CAPZA1	XM_011542225.4 linkuse as main transcript	c.101A>G	p.Asn34Ser	missense_variant, splice_region_variant	2/9		XP_011540527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPZA1	ENST00000263168.4 linkuse as main transcript	c.101A>G	p.Asn34Ser	missense_variant, splice_region_variant	2/10	1	NM_006135.3	ENSP00000263168.3	P52907
CAPZA1	ENST00000476936.5 linkuse as main transcript	n.127A>G		splice_region_variant, non_coding_transcript_exon_variant	2/8	3
CAPZA1	ENST00000485542.5 linkuse as main transcript	n.141A>G		splice_region_variant, non_coding_transcript_exon_variant	2/3	2
CAPZA1	ENST00000498626.1 linkuse as main transcript	n.154A>G		splice_region_variant, non_coding_transcript_exon_variant	3/9	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000854

AC:

AN:

222458

Hom.:

AF XY:

0.000124

AC XY:

AN XY:

121130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000659

Gnomad SAS exome

AF:

0.000633

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000954

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1331708

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

660514

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:

0.000855

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000971

Gnomad4 OTH exome

AF:

0.0000370

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.000115

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

Aug 19, 2024

The c.101A>G (p.N34S) alteration is located in exon 2 (coding exon 2) of the CAPZA1 gene. This alteration results from a A to G substitution at nucleotide position 101, causing the asparagine (N) at amino acid position 34 to be replaced by a serine (S). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

M_CAP

Benign

0.0027

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.19

Sift

Benign

0.16

Sift4G

Benign

0.25

Polyphen

0.11

Vest4

0.74

MVP

0.52

MPC

0.27

ClinPred

0.19

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.60

dbscSNV1_RF

Benign

0.48

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