rs61739642

Variant names:

• chr12-57243821-C-T
• rs61739642
• NM_145064.3:c.1086G>A
• STAC3 p.Glu362Glu

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_145064.3(STAC3):​c.1086G>A​(p.Glu362Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,614,008 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (41 hom.)
• Consequence: STAC3 NM_145064.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.37
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, Ambry Genetics, ClinGen

ENSG00000295078 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 12-57243821-C-T is Benign according to our data. Variant chr12-57243821-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.37 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1788/152330) while in subpopulation AFR AF = 0.0404 (1681/41574). AF 95% confidence interval is 0.0388. There are 32 homozygotes in GnomAd4. There are 844 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

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.1086G>A	p.Glu362Glu	synonymous	Exon 12 of 12	NP_659501.1	Q96MF2-1
	STAC3	NM_001286256.2		c.969G>A	p.Glu323Glu	synonymous	Exon 11 of 11	NP_001273185.1	Q96MF2-2
	STAC3	NM_001286257.2		c.528G>A	p.Glu176Glu	synonymous	Exon 9 of 9	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.1086G>A	p.Glu362Glu	synonymous	Exon 12 of 12	ENSP00000329200.2	Q96MF2-1
	STAC3	ENST00000554578.5	TSL:1	c.969G>A	p.Glu323Glu	synonymous	Exon 11 of 11	ENSP00000452068.1	Q96MF2-2
	STAC3	ENST00000557176.5	TSL:1	n.*146G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000450740.1	G3V2L9

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1783 AN: 152212 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

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: 0.00813

GnomAD2 exomes AF: 0.00301 AC: 754 AN: 250542 AF XY: 0.00211

Gnomad AFR exome AF: 0.0418

Gnomad AMR exome AF: 0.00168

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00120 AC: 1760 AN: 1461678 Hom.: 41 Cov.: 32 AF XY: 0.00103 AC XY: 747 AN XY: 727122

African (AFR) AF: 0.0438 AC: 1466 AN: 33470

American (AMR) AF: 0.00210 AC: 94 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5766

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111960

Other (OTH) AF: 0.00222 AC: 134 AN: 60380

GnomAD4 genome AF: 0.0117 AC: 1788 AN: 152330 Hom.: 32 Cov.: 32 AF XY: 0.0113 AC XY: 844 AN XY: 74484

African (AFR) AF: 0.0404 AC: 1681 AN: 41574

American (AMR) AF: 0.00555 AC: 85 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00580 Hom.: 9

Bravo AF: 0.0132

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bailey-Bloch congenital myopathy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		2.4
Mutation Taster		=80/20	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs61739642;

hg19: chr12-57637604;