NM_004055.5:c.865C>G

Variant names:

• chr11-77115560-C-G
• NM_004055.5:c.865C>G

Variant summary

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

The NM_004055.5(CAPN5):​c.865C>G​(p.Arg289Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,874 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CAPN5 NM_004055.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

Genes affected

CAPN5 (HGNC:1482): (calpain 5) Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3. [provided by RefSeq, Jul 2008]

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
CAPN5	NM_004055.5	c.865C>G	p.Arg289Gly	missense_variant	Exon 6 of 13	ENST00000648180.1	NP_004046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN5	ENST00000648180.1	c.865C>G	p.Arg289Gly	missense_variant	Exon 6 of 13		NM_004055.5	ENSP00000498132.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459874 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726204

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;D;D;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.88	.;.;D;D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.52	D;D;D;D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	-0.030	N;N;N;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.6	D;.;D;D;.
REVEL	Uncertain	0.46
Sift	Benign	0.18	T;.;T;T;.
Sift4G	Benign	0.19	T;.;T;T;.
Polyphen		0.93	P;P;P;B;.
Vest4		0.72
MutPred		0.58		.;.;.;Loss of MoRF binding (P = 0.0568);.;
MVP		0.89
MPC		0.68
ClinPred		0.98	D
GERP RS		3.1
Varity_R		0.69
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: chr11-76826606;