ENST00000557176.5:n.*157C>T

Variant names:

• chr12-57243810-G-A
• rs3204635
• ENST00000557176.5:n.*157C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000557176.5(STAC3):​n.*157C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,612,394 control chromosomes in the GnomAD database, including 66,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5116 hom., cov: 32)
  • Exomes 𝑓: 0.28 (61315 hom.)
• Consequence: STAC3 ENST00000557176.5 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.123
• Publications: 26 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 12-57243810-G-A is Benign according to our data. Variant chr12-57243810-G-A is described in ClinVar as Benign. ClinVar VariationId is 262568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557176.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAC3	NM_145064.3	MANE Select	c.*2C>T		3_prime_UTR	Exon 12 of 12	NP_659501.1
	STAC3	NR_104422.2		n.793C>T		non_coding_transcript_exon	Exon 8 of 8
	STAC3	NM_001286256.2		c.*2C>T		3_prime_UTR	Exon 11 of 11	NP_001273185.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAC3	ENST00000557176.5	TSL:1	n.*157C>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000450740.1
	STAC3	ENST00000332782.7	TSL:2 MANE Select	c.*2C>T		3_prime_UTR	Exon 12 of 12	ENSP00000329200.2
	STAC3	ENST00000554578.5	TSL:1	c.*2C>T		3_prime_UTR	Exon 11 of 11	ENSP00000452068.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37856 AN: 151976 Hom.: 5111 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.233

GnomAD2 exomes AF: 0.271 AC: 67649 AN: 249444 AF XY: 0.284

Gnomad AFR exome AF: 0.179

Gnomad AMR exome AF: 0.138

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.272

Gnomad OTH exome AF: 0.255

GnomAD4 exome AF: 0.283 AC: 413455 AN: 1460300 Hom.: 61315 Cov.: 34 AF XY: 0.288 AC XY: 209580 AN XY: 726466

African (AFR) AF: 0.171 AC: 5711 AN: 33456

American (AMR) AF: 0.146 AC: 6511 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5649 AN: 26110

East Asian (EAS) AF: 0.242 AC: 9616 AN: 39676

South Asian (SAS) AF: 0.434 AC: 37406 AN: 86178

European-Finnish (FIN) AF: 0.347 AC: 18477 AN: 53278

Middle Eastern (MID) AF: 0.170 AC: 980 AN: 5760

European-Non Finnish (NFE) AF: 0.281 AC: 312319 AN: 1110838

Other (OTH) AF: 0.278 AC: 16786 AN: 60326

GnomAD4 genome AF: 0.249 AC: 37878 AN: 152094 Hom.: 5116 Cov.: 32 AF XY: 0.256 AC XY: 19020 AN XY: 74328

African (AFR) AF: 0.178 AC: 7384 AN: 41500

American (AMR) AF: 0.198 AC: 3023 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3466

East Asian (EAS) AF: 0.243 AC: 1251 AN: 5152

South Asian (SAS) AF: 0.426 AC: 2059 AN: 4828

European-Finnish (FIN) AF: 0.362 AC: 3827 AN: 10564

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18895 AN: 67972

Other (OTH) AF: 0.238 AC: 504 AN: 2114

Alfa AF: 0.261 Hom.: 15592

Bravo AF: 0.225

Asia WGS AF: 0.293 AC: 1020 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 28, 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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs3204635; hg19: chr12-57637593; COSMIC: COSV60414735; COSMIC: COSV60414735;