1-112619878-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_006135.3(CAPZA1):c.34G>A(p.Glu12Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0037 in 1,611,892 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0038 (24 hom.)
• Consequence: CAPZA1 NM_006135.3 missense
• Clinical Significance: Benign/Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 6.19

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]

ST7L (HGNC:18441): (suppression of tumorigenicity 7 like) This gene was identified by its similarity to the ST7 tumor suppressor gene found in the chromosome 7q31 region. This gene is clustered in a tail-to-tail manner with the WNT2B gene in a chromosomal region known to be deleted and rearranged in a variety of cancers. Several transcript variants encoding many different isoforms have been described, but some have not been fully characterized. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012323827).
• BP6: Variant 1-112619878-G-A is Benign according to our data. Variant chr1-112619878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1206064.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-112619878-G-A is described in Lovd as [Benign]. Variant chr1-112619878-G-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 343 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAPZA1	NM_006135.3	c.34G>A	p.Glu12Lys	missense_variant	1/10	ENST00000263168.4
CAPZA1	XM_017002424.3	c.34G>A	p.Glu12Lys	missense_variant	1/10
CAPZA1	XM_011542225.4	c.34G>A	p.Glu12Lys	missense_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAPZA1	ENST00000263168.4	c.34G>A	p.Glu12Lys	missense_variant	1/10	1	NM_006135.3	P1

Frequencies

GnomAD3 genomes AF: 0.00225 AC: 343 AN: 152228 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00340

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00193 AC: 472 AN: 244770 Hom.: 5 AF XY: 0.00203 AC XY: 270 AN XY: 132836

Gnomad AFR exome AF: 0.000779

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.000303

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000938

Gnomad FIN exome AF: 0.000434

Gnomad NFE exome AF: 0.00335

Gnomad OTH exome AF: 0.00151

GnomAD4 exome AF: 0.00385 AC: 5619 AN: 1459546 Hom.: 24 Cov.: 30 AF XY: 0.00376 AC XY: 2731 AN XY: 725964

Gnomad4 AFR exome AF: 0.000598

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000863

Gnomad4 FIN exome AF: 0.000433

Gnomad4 NFE exome AF: 0.00474

Gnomad4 OTH exome AF: 0.00280

GnomAD4 genome AF: 0.00225 AC: 343 AN: 152346 Hom.: 2 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74504

Gnomad4 AFR AF: 0.000649

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00340

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00332 Hom.: 2

Bravo AF: 0.00244

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00384 AC: 33

ExAC AF: 0.00182 AC: 221

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

-

- -

not provided Benign:1

Likely benign, no assertion criteria provided

clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Pathogenic	0.28
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.26
Sift	Benign	0.073	T
Sift4G	Benign	0.11	T
Polyphen		0.0010	B
Vest4		0.62
MVP		0.85
MPC		0.32
ClinPred		0.030	T
GERP RS		6.2
Varity_R		0.59
gMVP		0.71

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

Other links and lift over

dbSNP: rs149653791; hg19: chr1-113162500;