X-111251300-GAAA-G

Variant names:

• chrX-111251300-GAAA-G
• NM_014289.4:c.894-17_894-15delTTT

Variant summary

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

The NM_014289.4(CAPN6):​c.894-17_894-15delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000286 in 840,332 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.000029 (0 hom. 0 hem.)
• Consequence: CAPN6 NM_014289.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.31

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

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
CAPN6	NM_014289.4	c.894-17_894-15delTTT		intron_variant	Intron 6 of 12	ENST00000324068.2	NP_055104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN6	ENST00000324068.2	c.894-17_894-15delTTT		intron_variant	Intron 6 of 12	1	NM_014289.4	ENSP00000317214.1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.0000286 AC: 24 AN: 840332 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 253544

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000650

Gnomad4 EAS exome AF: 0.0000388

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000299

Gnomad4 NFE exome AF: 0.0000326

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: chrX-110494528;