rs1555420773

Variant names:

• chr15-42390025-A-G
• NM_000070.3:c.874A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-42390025-A-G
• chr15-42390025-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000070.3(CAPN3):​c.874A>G​(p.Arg292Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAPN3 NM_000070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.52

Genes affected

CAPN3 (HGNC:1480): (calpain 3) Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]

ENSG00000258461 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN3	NM_000070.3	c.874A>G	p.Arg292Gly	missense_variant	Exon 6 of 24	ENST00000397163.8	NP_000061.1
CAPN3	NM_024344.2	c.874A>G	p.Arg292Gly	missense_variant	Exon 6 of 23		NP_077320.1
CAPN3	NM_173087.2	c.801+929A>G		intron_variant	Intron 5 of 20		NP_775110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN3	ENST00000397163.8	c.874A>G	p.Arg292Gly	missense_variant	Exon 6 of 24	1	NM_000070.3	ENSP00000380349.3
ENSG00000258461	ENST00000495723.1	n.*670A>G		non_coding_transcript_exon_variant	Exon 10 of 26	2		ENSP00000492063.1
ENSG00000258461	ENST00000495723.1	n.*670A>G		3_prime_UTR_variant	Exon 10 of 26	2		ENSP00000492063.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.43	T;T
MetaSVM	Uncertain	-0.054	T
MutationAssessor	Benign	-0.20	N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.52
Sift	Uncertain	0.0080	D;D
Sift4G	Benign	0.30	T;T
Polyphen		0.043	B;B
Vest4		0.52
MutPred		0.67		Loss of catalytic residue at M290 (P = 0.0325);Loss of catalytic residue at M290 (P = 0.0325);
MVP		0.91
MPC		0.18
ClinPred		0.60	D
GERP RS		5.9
Varity_R		0.20
gMVP		0.64

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42682223; COSMIC: COSV105181285;