1-112647239-T-C

Variant names:

• chr1-112647239-T-C
• rs1203793665
• NM_006135.3:c.69T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006135.3(CAPZA1):​c.69T>C​(p.His23His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,379,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CAPZA1 NM_006135.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).

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.69T>C	p.His23His	synonymous	Exon 2 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.69T>C	p.His23His	synonymous	Exon 2 of 10	ENSP00000263168.3	P52907
	CAPZA1	ENST00000904626.1		c.69T>C	p.His23His	synonymous	Exon 2 of 10	ENSP00000574685.1
	CAPZA1	ENST00000917728.1		c.69T>C	p.His23His	synonymous	Exon 2 of 11	ENSP00000587787.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000435 AC: 1 AN: 229686 AF XY: 0.00

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: 0.000185

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1379196 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 684488

African (AFR) AF: 0.00 AC: 0 AN: 31666

American (AMR) AF: 0.00 AC: 0 AN: 39622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24112

East Asian (EAS) AF: 0.00 AC: 0 AN: 37340

South Asian (SAS) AF: 0.00 AC: 0 AN: 71256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49740

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5362

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063908

Other (OTH) AF: 0.0000178 AC: 1 AN: 56190

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=85/15	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: rs1203793665; hg19: chr1-113189861;