NM_145064.3:c.604-8C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_145064.3(STAC3):c.604-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00933 in 1,613,798 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 186 hom. )

Consequence

STAC3
NM_145064.3 splice_region, intron

Scores

Splicing: ADA: 0.0008489

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.14

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 12-57245219-G-A is Benign according to our data. Variant chr12-57245219-G-A is described in ClinVar as Benign. ClinVar VariationId is 262576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC3	NM_145064.3 link	c.604-8C>T		splice_region_variant, intron_variant	Intron 6 of 11	ENST00000332782.7	NP_659501.1	Q96MF2-1A0A024RB38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAC3	ENST00000332782.7 link	c.604-8C>T		splice_region_variant, intron_variant	Intron 6 of 11	2	NM_145064.3	ENSP00000329200.2		Q96MF2-1

Frequencies

GnomAD3 genomes

AF:

0.00891

AC:

1355

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00908

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00657

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.0109

AC:

2737

AN:

250826

AF XY:

0.0111

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.0666

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00576

Gnomad OTH exome

AF:

0.00639

GnomAD4 exome

AF:

0.00937

AC:

13692

AN:

1461556

Hom.:

186

Cov.:

AF XY:

0.00952

AC XY:

6920

AN XY:

727076

show subpopulations

African (AFR)

AF:

0.00974

AC:

326

AN:

33474

American (AMR)

AF:

0.00148

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00574

AC:

150

AN:

26120

East Asian (EAS)

AF:

0.0728

AC:

2889

AN:

39686

South Asian (SAS)

AF:

0.0185

AC:

1598

AN:

86194

European-Finnish (FIN)

AF:

0.00155

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00832

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00709

AC:

7884

AN:

1111832

Other (OTH)

AF:

0.0107

AC:

648

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

637

1274

1912

2549

3186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.00892

AC:

1358

AN:

152242

Hom.:

Cov.:

AF XY:

0.00993

AC XY:

739

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00912

AC:

379

AN:

41536

American (AMR)

AF:

0.00170

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.0719

AC:

371

AN:

5160

South Asian (SAS)

AF:

0.0216

AC:

104

AN:

4822

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00657

AC:

447

AN:

68020

Other (OTH)

AF:

0.00569

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00610

Hom.:

Bravo

AF:

0.00940

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bailey-Bloch congenital myopathy

Benign:1

Jan 30, 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

-0.42

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00085

dbscSNV1_RF

Benign

0.050

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over