rs76667525

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145064.3(STAC3):​c.570G>C​(p.Lys190Asn) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K190K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: STAC3 NM_145064.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3964823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC3	NM_145064.3	c.570G>C	p.Lys190Asn	missense_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>C	p.Lys190Asn	missense_variant	Exon 6 of 12	2	NM_145064.3	ENSP00000329200.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Benign	1.8	.;L;.
PhyloP100		0.97
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.045	D;D;D
Sift4G	Benign	0.072	T;T;D
Polyphen		1.0	.;D;.
Vest4		0.45
MutPred		0.42		.;Gain of catalytic residue at V185 (P = 0);.;
MVP		0.81
MPC		1.1
ClinPred		0.87	D
GERP RS		2.2
Varity_R		0.25
gMVP		0.47
Mutation Taster		=44/56	disease causing

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;