NM_145064.3:c.1014A>G

Variant names:

• chr12-57243893-T-C
• rs376366403
• NM_145064.3:c.1014A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_145064.3(STAC3):​c.1014A>G​(p.Gly338Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAC3 NM_145064.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 12-57243893-T-C is Benign according to our data. Variant chr12-57243893-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1108618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.169 with no splicing effect.

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.1014A>G	p.Gly338Gly	synonymous	Exon 12 of 12	NP_659501.1	Q96MF2-1
	STAC3	NM_001286256.2		c.897A>G	p.Gly299Gly	synonymous	Exon 11 of 11	NP_001273185.1	Q96MF2-2
	STAC3	NM_001286257.2		c.456A>G	p.Gly152Gly	synonymous	Exon 9 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.1014A>G	p.Gly338Gly	synonymous	Exon 12 of 12	ENSP00000329200.2	Q96MF2-1
	STAC3	ENST00000554578.5	TSL:1	c.897A>G	p.Gly299Gly	synonymous	Exon 11 of 11	ENSP00000452068.1	Q96MF2-2
	STAC3	ENST00000557176.5	TSL:1	n.*74A>G		non_coding_transcript_exon	Exon 8 of 8	ENSP00000450740.1	G3V2L9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250354 AF XY: 0.00000738

Gnomad AFR exome AF: 0.0000622

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Bailey-Bloch congenital myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.17

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

Other links and lift over

dbSNP: rs376366403; hg19: chr12-57637676;