X-111251300-GAAA-GAAAAAAAA

Variant names:

• chrX-111251300-G-GAAAAA
• rs201147886
• NM_014289.4:c.894-19_894-15dupTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014289.4(CAPN6):​c.894-19_894-15dupTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: CAPN6 NM_014289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31
• Publications: 0 publications found

Genes affected

CAPN6 (HGNC:1483): (calpain 6) Calpains are 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 subunit possesses a cysteine protease domain, and both subunits possess calcium-binding domains. Calpains have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. The protein encoded by this gene is highly expressed in the placenta. Its C-terminal region lacks any homology to the calmodulin-like domain of other calpains. The protein lacks critical active site residues and thus is suggested to be proteolytically inactive. The protein may play a role in tumor formation by inhibiting apoptosis and promoting angiogenesis. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014289.4. 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
	CAPN6	NM_014289.4	MANE Select	c.894-19_894-15dupTTTTT		intron	N/A	NP_055104.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPN6	ENST00000324068.2	TSL:1 MANE Select	c.894-15_894-14insTTTTT		intron	N/A	ENSP00000317214.1	Q9Y6Q1
	CAPN6	ENST00000932651.1		c.492-15_492-14insTTTTT		intron	N/A	ENSP00000602710.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.00000119 AC: 1 AN: 841472 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 254106

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20070

American (AMR) AF: 0.00 AC: 0 AN: 22423

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15396

East Asian (EAS) AF: 0.00 AC: 0 AN: 25777

South Asian (SAS) AF: 0.00 AC: 0 AN: 39091

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33529

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2900

European-Non Finnish (NFE) AF: 0.00000155 AC: 1 AN: 645897

Other (OTH) AF: 0.00 AC: 0 AN: 36389

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

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

Other links and lift over

dbSNP: rs201147886; hg19: chrX-110494528;