Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145064.3(STAC3):c.1023G>C(p.Ala341Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,613,814 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A341A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 30 hom. )

Consequence

STAC3
NM_145064.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.27

Publications

2 publications found

Variant links:

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

STAC3 links:

ENSG00000295078 (HGNC:):

ENSG00000295078 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 12-57243884-C-G is Benign according to our data. Variant chr12-57243884-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.27 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00431 (656/152174) while in subpopulation AMR AF = 0.00444 (68/15302). AF 95% confidence interval is 0.00376. There are 3 homozygotes in GnomAd4. There are 380 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAC3	NM_145064.3	MANE Select	c.1023G>C	p.Ala341Ala	synonymous	Exon 12 of 12	NP_659501.1
STAC3	NM_001286256.2		c.906G>C	p.Ala302Ala	synonymous	Exon 11 of 11	NP_001273185.1
STAC3	NM_001286257.2		c.465G>C	p.Ala155Ala	synonymous	Exon 9 of 9	NP_001273186.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STAC3	ENST00000332782.7	TSL:2 MANE Select	c.1023G>C	p.Ala341Ala	synonymous	Exon 12 of 12	ENSP00000329200.2
STAC3	ENST00000554578.5	TSL:1	c.906G>C	p.Ala302Ala	synonymous	Exon 11 of 11	ENSP00000452068.1
STAC3	ENST00000557176.5	TSL:1	n.*83G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000450740.1

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

656

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00416

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00449

AC:

1124

AN:

250332

AF XY:

0.00466

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.00270

Gnomad ASJ exome

AF:

0.00269

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0224

Gnomad NFE exome

AF:

0.00403

Gnomad OTH exome

AF:

0.00442

GnomAD4 exome

AF:

0.00387

AC:

5654

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

2835

AN XY:

727108

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33478

American (AMR)

AF:

0.00278

AC:

124

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00299

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00157

AC:

135

AN:

86240

European-Finnish (FIN)

AF:

0.0208

AC:

1109

AN:

53338

Middle Eastern (MID)

AF:

0.00121

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00357

AC:

3971

AN:

1111948

Other (OTH)

AF:

0.00359

AC:

217

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

329

659

988

1318

1647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00431

AC:

656

AN:

152174

Hom.:

Cov.:

AF XY:

0.00511

AC XY:

380

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

41500

American (AMR)

AF:

0.00444

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00375

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00125

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0222

AC:

235

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00416

AC:

283

AN:

68002

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

126

158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00311

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00327

EpiControl

AF:

0.00350

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Bailey-Bloch congenital myopathy (1)

not specified (1)

STAC3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.2

(source)

DANN

Benign

0.77

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs61747067

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over