rs80212483

Variant names:

• chr12-57243934-T-C
• rs80212483
• NM_145064.3:c.997-24A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57243934-T-C
• chr12-57243934-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145064.3(STAC3):​c.997-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,611,978 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0025 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (78 hom.)
• Consequence: STAC3 NM_145064.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.612
• Publications: 5 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: PanelApp Australia, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000295078 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-57243934-T-C is Benign according to our data. Variant chr12-57243934-T-C is described in ClinVar as Benign. ClinVar VariationId is 1222559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145064.3. 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
	STAC3	NM_145064.3	MANE Select	c.997-24A>G		intron	N/A	NP_659501.1	Q96MF2-1
	STAC3	NM_001286256.2		c.880-24A>G		intron	N/A	NP_001273185.1	Q96MF2-2
	STAC3	NM_001286257.2		c.439-24A>G		intron	N/A	NP_001273186.1	Q96MF2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAC3	ENST00000332782.7	TSL:2 MANE Select	c.997-24A>G		intron	N/A	ENSP00000329200.2	Q96MF2-1
	STAC3	ENST00000554578.5	TSL:1	c.880-24A>G		intron	N/A	ENSP00000452068.1	Q96MF2-2
	STAC3	ENST00000557176.5	TSL:1	n.*57-24A>G		intron	N/A	ENSP00000450740.1	G3V2L9

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 386 AN: 151956 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00866

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00551 AC: 1357 AN: 246452 AF XY: 0.00512

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.0648

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000279

Gnomad OTH exome AF: 0.00316

GnomAD4 exome AF: 0.00219 AC: 3201 AN: 1459904 Hom.: 78 Cov.: 32 AF XY: 0.00217 AC XY: 1574 AN XY: 726224

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.000270 AC: 12 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.0103 AC: 269 AN: 26070

East Asian (EAS) AF: 0.0646 AC: 2563 AN: 39674

South Asian (SAS) AF: 0.00101 AC: 87 AN: 86042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.000522 AC: 3 AN: 5752

European-Non Finnish (NFE) AF: 0.0000765 AC: 85 AN: 1111034

Other (OTH) AF: 0.00302 AC: 182 AN: 60296

GnomAD4 genome AF: 0.00253 AC: 385 AN: 152074 Hom.: 8 Cov.: 32 AF XY: 0.00269 AC XY: 200 AN XY: 74318

African (AFR) AF: 0.0000482 AC: 2 AN: 41472

American (AMR) AF: 0.000327 AC: 5 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00866 AC: 30 AN: 3466

East Asian (EAS) AF: 0.0613 AC: 317 AN: 5172

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 67986

Other (OTH) AF: 0.00380 AC: 8 AN: 2104

Alfa AF: 0.00285 Hom.: 6

Bravo AF: 0.00317

Asia WGS AF: 0.0180 AC: 65 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.73
PhyloP100		-0.61
La Branchor		0.65
BranchPoint Hunter		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs80212483; hg19: chr12-57637717; COSMIC: COSV107409097; COSMIC: COSV107409097;