12-57243967-ACAG-A

Position:

• chr12-57243967-ACAG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_145064.3(STAC3):​c.997-60_997-58del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,607,524 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (42 hom.)
• Consequence: STAC3 NM_145064.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13

Genes affected

STAC3 (HGNC:28423): (SH3 and cysteine rich domain 3) The protein encoded by this gene is a component of the excitation-contraction coupling machinery of muscles. This protein is a member of the Stac gene family and contains an N-terminal cysteine-rich domain and two SH3 domains. Mutations in this gene are a cause of Native American myopathy. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-57243967-ACAG-A is Benign according to our data. Variant chr12-57243967-ACAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1301206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0118 (1796/152290) while in subpopulation AFR AF= 0.0406 (1688/41556). AF 95% confidence interval is 0.039. There are 33 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAC3	NM_145064.3	c.997-60_997-58del		intron_variant		ENST00000332782.7	NP_659501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAC3	ENST00000332782.7	c.997-60_997-58del		intron_variant		2	NM_145064.3	ENSP00000329200	P1
STAC3	ENST00000554578.5	c.880-60_880-58del		intron_variant		1		ENSP00000452068
STAC3	ENST00000557176.5	c.*57-60_*57-58del		intron_variant, NMD_transcript_variant		1		ENSP00000450740
STAC3	ENST00000546246.2	c.439-60_439-58del		intron_variant		2		ENSP00000441515

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1791 AN: 152172 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00120 AC: 1751 AN: 1455234 Hom.: 42 AF XY: 0.00103 AC XY: 746 AN XY: 723668

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.00214

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000466

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000433

Gnomad4 OTH exome AF: 0.00223

GnomAD4 genome AF: 0.0118 AC: 1796 AN: 152290 Hom.: 33 Cov.: 32 AF XY: 0.0114 AC XY: 849 AN XY: 74468

Gnomad4 AFR AF: 0.0406

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00821 Hom.: 1

Bravo AF: 0.0133

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs141957095; hg19: chr12-57637750;