rs76667525

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-57246837-C-T
• chr12-57246837-C-G

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: PanelApp Australia, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 VariationId 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.

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.570G>A	p.Lys190Lys	synonymous	Exon 6 of 12	NP_659501.1	Q96MF2-1
	STAC3	NM_001286256.2		c.453G>A	p.Lys151Lys	synonymous	Exon 5 of 11	NP_001273185.1	Q96MF2-2
	STAC3	NM_001286257.2		c.12G>A	p.Lys4Lys	synonymous	Exon 3 of 9	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.570G>A	p.Lys190Lys	synonymous	Exon 6 of 12	ENSP00000329200.2	Q96MF2-1
	STAC3	ENST00000554578.5	TSL:1	c.453G>A	p.Lys151Lys	synonymous	Exon 5 of 11	ENSP00000452068.1	Q96MF2-2
	STAC3	ENST00000557176.5	TSL:1	n.12G>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000450740.1	G3V2L9

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Bailey-Bloch congenital myopathy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;