12-57246837-C-T

Variant names:

• chr12-57246837-C-T
• rs76667525
• NM_145064.3:c.570G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_145064.3(STAC3):​c.570G>A​(p.Lys190Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00933 in 1,613,976 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0089 (22 hom., cov: 31)
  • Exomes 𝑓: 0.0094 (187 hom.)
• Consequence: STAC3 NM_145064.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.971
• Publications: 5 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 12-57246837-C-T is Benign according to our data. Variant chr12-57246837-C-T is described in ClinVar as [Benign]. Clinvar id is 262575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.971 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC3	NM_145064.3	c.570G>A	p.Lys190Lys	synonymous_variant	Exon 6 of 12	ENST00000332782.7	NP_659501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAC3	ENST00000332782.7	c.570G>A	p.Lys190Lys	synonymous_variant	Exon 6 of 12	2	NM_145064.3	ENSP00000329200.2

Frequencies

GnomAD3 genomes AF: 0.00894 AC: 1360 AN: 152174 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.00910

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0723

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.0109 AC: 2732 AN: 251472 AF XY: 0.0111

Gnomad AFR exome AF: 0.00837

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.00446

Gnomad EAS exome AF: 0.0664

Gnomad FIN exome AF: 0.00189

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.00635

GnomAD4 exome AF: 0.00937 AC: 13699 AN: 1461684 Hom.: 187 Cov.: 30 AF XY: 0.00952 AC XY: 6923 AN XY: 727148

African (AFR) AF: 0.00965 AC: 323 AN: 33476

American (AMR) AF: 0.00148 AC: 66 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00574 AC: 150 AN: 26136

East Asian (EAS) AF: 0.0727 AC: 2884 AN: 39680

South Asian (SAS) AF: 0.0185 AC: 1596 AN: 86248

European-Finnish (FIN) AF: 0.00155 AC: 83 AN: 53410

Middle Eastern (MID) AF: 0.00833 AC: 48 AN: 5764

European-Non Finnish (NFE) AF: 0.00710 AC: 7898 AN: 1111866

Other (OTH) AF: 0.0108 AC: 651 AN: 60386

GnomAD4 genome AF: 0.00894 AC: 1362 AN: 152292 Hom.: 22 Cov.: 31 AF XY: 0.00996 AC XY: 742 AN XY: 74464

African (AFR) AF: 0.00912 AC: 379 AN: 41558

American (AMR) AF: 0.00170 AC: 26 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5178

South Asian (SAS) AF: 0.0218 AC: 105 AN: 4822

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10618

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

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68030

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00640 Hom.: 4

Bravo AF: 0.00938

Asia WGS AF: 0.0510 AC: 177 AN: 3478

EpiCase AF: 0.00649

EpiControl AF: 0.00563

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.32
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.97
Mutation Taster		=90/10	polymorphism (auto)

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: rs76667525; hg19: chr12-57640620;