NM_023083.4:c.1860G>A

Variant names:

• chr2-240598004-G-A
• rs3749166
• NM_023083.4:c.1860G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_023083.4(CAPN10):​c.1860G>A​(p.Ala620Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,612,786 control chromosomes in the GnomAD database, including 287,257 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (22198 hom., cov: 33)
  • Exomes 𝑓: 0.60 (265059 hom.)
• Consequence: CAPN10 NM_023083.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 26 publications found

Genes affected

CAPN10 (HGNC:1477): (calpain 10) Calpains represent a ubiquitous, well-conserved family of calcium-dependent cysteine proteases. The calpain proteins are heterodimers consisting of an invariant small subunit and variable large subunits. The large catalytic subunit has four domains: domain I, the N-terminal regulatory domain that is processed upon calpain activation; domain II, the protease domain; domain III, a linker domain of unknown function; and domain IV, the calmodulin-like calcium-binding domain. This gene encodes a large subunit. It is an atypical calpain in that it lacks the calmodulin-like calcium-binding domain and instead has a divergent C-terminal domain. It is similar in organization to calpains 5 and 6. This gene is associated with type 2 or non-insulin-dependent diabetes mellitus (NIDDM), and is located within the NIDDM1 region. Multiple alternative transcript variants have been described for this gene. [provided by RefSeq, Sep 2010]

CAPN10 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023083.4. 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
	CAPN10	NM_023083.4	MANE Select	c.1860G>A	p.Ala620Ala	synonymous	Exon 10 of 12	NP_075571.2	Q9HC96-1
	CAPN10	NM_023085.4		c.1395G>A	p.Ala465Ala	synonymous	Exon 8 of 10	NP_075573.3	Q9HC96-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN10	ENST00000391984.7	TSL:1 MANE Select	c.1860G>A	p.Ala620Ala	synonymous	Exon 10 of 12	ENSP00000375844.2	Q9HC96-1
	CAPN10	ENST00000354082.8	TSL:1	c.1395G>A	p.Ala465Ala	synonymous	Exon 8 of 10	ENSP00000270362.6	Q9HC96-3
	CAPN10	ENST00000352879.8	TSL:1	c.258G>A	p.Ala86Ala	synonymous	Exon 2 of 4	ENSP00000289381.6	Q9HC96-8

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79636 AN: 151872 Hom.: 22182 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.554

GnomAD2 exomes AF: 0.583 AC: 145961 AN: 250162 AF XY: 0.589

Gnomad AFR exome AF: 0.309

Gnomad AMR exome AF: 0.606

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.659

Gnomad FIN exome AF: 0.542

Gnomad NFE exome AF: 0.613

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.600 AC: 875966 AN: 1460796 Hom.: 265059 Cov.: 55 AF XY: 0.600 AC XY: 436128 AN XY: 726736

African (AFR) AF: 0.300 AC: 10050 AN: 33480

American (AMR) AF: 0.604 AC: 27011 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 15580 AN: 26126

East Asian (EAS) AF: 0.645 AC: 25586 AN: 39698

South Asian (SAS) AF: 0.573 AC: 49388 AN: 86246

European-Finnish (FIN) AF: 0.552 AC: 29010 AN: 52598

Middle Eastern (MID) AF: 0.517 AC: 2981 AN: 5766

European-Non Finnish (NFE) AF: 0.612 AC: 680538 AN: 1111788

Other (OTH) AF: 0.593 AC: 35822 AN: 60382

GnomAD4 genome AF: 0.524 AC: 79684 AN: 151990 Hom.: 22198 Cov.: 33 AF XY: 0.524 AC XY: 38953 AN XY: 74282

African (AFR) AF: 0.320 AC: 13277 AN: 41458

American (AMR) AF: 0.577 AC: 8826 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2103 AN: 3470

East Asian (EAS) AF: 0.658 AC: 3388 AN: 5150

South Asian (SAS) AF: 0.566 AC: 2727 AN: 4818

European-Finnish (FIN) AF: 0.551 AC: 5824 AN: 10572

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41543 AN: 67920

Other (OTH) AF: 0.556 AC: 1175 AN: 2112

Alfa AF: 0.578 Hom.: 21281

Bravo AF: 0.518

Asia WGS AF: 0.594 AC: 2062 AN: 3478

EpiCase AF: 0.602

EpiControl AF: 0.601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.58
PhyloP100		-2.3
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.44		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3749166; hg19: chr2-241537421; COSMIC: COSV54375427; COSMIC: COSV54375427;