1-112647213-C-G

Variant names:

• chr1-112647213-C-G
• NM_006135.3:c.43C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006135.3(CAPZA1):​c.43C>G​(p.Arg15Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000736 in 1,358,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: CAPZA1 NM_006135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPZA1	NM_006135.3	c.43C>G	p.Arg15Gly	missense_variant	Exon 2 of 10	ENST00000263168.4	NP_006126.1
CAPZA1	XM_017002424.3	c.43C>G	p.Arg15Gly	missense_variant	Exon 2 of 10		XP_016857913.1
CAPZA1	XM_011542225.4	c.43C>G	p.Arg15Gly	missense_variant	Exon 2 of 9		XP_011540527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPZA1	ENST00000263168.4	c.43C>G	p.Arg15Gly	missense_variant	Exon 2 of 10	1	NM_006135.3	ENSP00000263168.3
CAPZA1	ENST00000476936.5	n.69C>G		non_coding_transcript_exon_variant	Exon 2 of 8	3
CAPZA1	ENST00000485542.5	n.83C>G		non_coding_transcript_exon_variant	Exon 2 of 3	2
CAPZA1	ENST00000498626.1	n.96C>G		non_coding_transcript_exon_variant	Exon 3 of 9	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.36e-7 AC: 1 AN: 1358366 Hom.: 0 Cov.: 25 AF XY: 0.00000148 AC XY: 1 AN XY: 673926

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.54e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.56
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0050	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.031	D
Polyphen		0.076	B
Vest4		0.84
MutPred		0.59		Gain of ubiquitination at K19 (P = 0.0505);
MVP		0.77
MPC		0.55
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.80
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.54		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.54		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-113189835;