rs148939626

Variant names:

• chr12-57249117-G-A
• rs148939626
• NM_145064.3:c.258C>T
• STAC3 p.Asn86Asn

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_145064.3(STAC3):​c.258C>T​(p.Asn86Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000942 in 1,613,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000096 (0 hom.)
• Consequence: STAC3 NM_145064.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.153
• Publications: 3 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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia, Ambry Genetics, G2P

ENSG00000295078 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 12-57249117-G-A is Benign according to our data. Variant chr12-57249117-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 262572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.

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.258C>T	p.Asn86Asn	synonymous	Exon 3 of 12	NP_659501.1	Q96MF2-1
	STAC3	NM_001286256.2		c.141C>T	p.Asn47Asn	synonymous	Exon 2 of 11	NP_001273185.1	Q96MF2-2
	STAC3	NM_001286257.2		c.-126-919C>T		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.258C>T	p.Asn86Asn	synonymous	Exon 3 of 12	ENSP00000329200.2	Q96MF2-1
	STAC3	ENST00000554578.5	TSL:1	c.141C>T	p.Asn47Asn	synonymous	Exon 2 of 11	ENSP00000452068.1	Q96MF2-2
	STAC3	ENST00000557176.5	TSL:1	n.-126-919C>T		intron	N/A	ENSP00000450740.1	G3V2L9

Frequencies

GnomAD3 genomes AF: 0.0000789 AC: 12 AN: 152150 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000725 AC: 18 AN: 248120 AF XY: 0.0000372

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.000135

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000958 AC: 140 AN: 1461270 Hom.: 0 Cov.: 31 AF XY: 0.0000949 AC XY: 69 AN XY: 726918

African (AFR) AF: 0.0000598 AC: 2 AN: 33454

American (AMR) AF: 0.0000224 AC: 1 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1111764

Other (OTH) AF: 0.000133 AC: 8 AN: 60376

GnomAD4 genome AF: 0.0000789 AC: 12 AN: 152150 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000793

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.2
DANN	Benign	0.82
PhyloP100		-0.15

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: rs148939626;

hg19: chr12-57642900;

COSMIC: COSV60413795;

COSMIC: COSV60413795;