12-57243967-ACAG-A

Variant names:

• chr12-57243967-ACAG-A
• rs141957095
• NM_145064.3:c.997-60_997-58delCTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_145064.3(STAC3):​c.997-60_997-58delCTG 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
• Publications: 0 publications found

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]

STAC3 Gene-Disease associations (from GenCC):

• Bailey-Bloch congenital myopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen, G2P

ENSG00000295078 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC3	NM_145064.3	c.997-60_997-58delCTG		intron_variant	Intron 11 of 11	ENST00000332782.7	NP_659501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAC3	ENST00000332782.7	c.997-60_997-58delCTG		intron_variant	Intron 11 of 11	2	NM_145064.3	ENSP00000329200.2

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

African (AFR) AF: 0.0439 AC: 1459 AN: 33200

American (AMR) AF: 0.00214 AC: 94 AN: 43856

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25962

East Asian (EAS) AF: 0.00 AC: 0 AN: 39546

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53086

Middle Eastern (MID) AF: 0.00194 AC: 11 AN: 5660

European-Non Finnish (NFE) AF: 0.0000433 AC: 48 AN: 1108066

Other (OTH) AF: 0.00223 AC: 134 AN: 60088

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

African (AFR) AF: 0.0406 AC: 1688 AN: 41556

American (AMR) AF: 0.00562 AC: 86 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68024

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

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

Mar 29, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=100/0	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: rs141957095; hg19: chr12-57637750;