1-112654609-G-A

Variant names:

• chr1-112654609-G-A
• rs778675866
• NM_006135.3:c.364G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006135.3(CAPZA1):​c.364G>A​(p.Glu122Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (1 hom.)
• Consequence: CAPZA1 NM_006135.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16281325).
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006135.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZA1	NM_006135.3	MANE Select	c.364G>A	p.Glu122Lys	missense	Exon 5 of 10	NP_006126.1	P52907

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPZA1	ENST00000263168.4	TSL:1 MANE Select	c.364G>A	p.Glu122Lys	missense	Exon 5 of 10	ENSP00000263168.3	P52907
	CAPZA1	ENST00000904626.1		c.364G>A	p.Glu122Lys	missense	Exon 5 of 10	ENSP00000574685.1
	CAPZA1	ENST00000917728.1		c.364G>A	p.Glu122Lys	missense	Exon 5 of 11	ENSP00000587787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250958 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461706 Hom.: 1 Cov.: 30 AF XY: 0.00000963 AC XY: 7 AN XY: 727164

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.26	N
PhyloP100		4.7
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.053
Sift	Benign	0.72	T
Sift4G	Benign	0.84	T
Polyphen		0.033	B
Vest4		0.31
MutPred		0.52		Gain of MoRF binding (P = 0.0048)
MVP		0.28
MPC		0.29
ClinPred		0.41	T
GERP RS		4.6
Varity_R		0.21
gMVP		0.23
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs778675866; hg19: chr1-113197231;