12-57244071-T-A

Variant names:

• chr12-57244071-T-A
• rs150268069
• NM_145064.3:c.996+17A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145064.3(STAC3):​c.996+17A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,870 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (6 hom., cov: 32)
  • Exomes 𝑓: 0.012 (154 hom.)
• Consequence: STAC3 NM_145064.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.26
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-57244071-T-A is Benign according to our data. Variant chr12-57244071-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 262578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00786 (1195/152068) while in subpopulation NFE AF = 0.014 (949/67986). AF 95% confidence interval is 0.0132. There are 6 homozygotes in GnomAd4. There are 538 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC3	NM_145064.3	c.996+17A>T		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.996+17A>T		intron_variant	Intron 11 of 11	2	NM_145064.3	ENSP00000329200.2

Frequencies

GnomAD3 genomes AF: 0.00786 AC: 1195 AN: 151950 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00302

Gnomad ASJ AF: 0.00434

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.00680

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00962 AC: 2415 AN: 251140 AF XY: 0.00974

Gnomad AFR exome AF: 0.00166

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00878

Gnomad NFE exome AF: 0.0166

Gnomad OTH exome AF: 0.00654

GnomAD4 exome AF: 0.0119 AC: 17426 AN: 1461802 Hom.: 154 Cov.: 32 AF XY: 0.0116 AC XY: 8454 AN XY: 727188

African (AFR) AF: 0.00146 AC: 49 AN: 33480

American (AMR) AF: 0.00163 AC: 73 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00337 AC: 88 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00646 AC: 557 AN: 86250

European-Finnish (FIN) AF: 0.00959 AC: 512 AN: 53384

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0141 AC: 15629 AN: 1111980

Other (OTH) AF: 0.00849 AC: 513 AN: 60392

GnomAD4 genome AF: 0.00786 AC: 1195 AN: 152068 Hom.: 6 Cov.: 32 AF XY: 0.00724 AC XY: 538 AN XY: 74332

African (AFR) AF: 0.00195 AC: 81 AN: 41488

American (AMR) AF: 0.00301 AC: 46 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00434 AC: 15 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4808

European-Finnish (FIN) AF: 0.00680 AC: 72 AN: 10586

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

European-Non Finnish (NFE) AF: 0.0140 AC: 949 AN: 67986

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00994 Hom.: 0

Bravo AF: 0.00737

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 23, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bailey-Bloch congenital myopathy Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.66
DANN	Benign	0.48
PhyloP100		-1.3
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: rs150268069; hg19: chr12-57637854;