11-69049014-CG-TC

Variant names:

• chr11-69049014-CG-TC
• NM_139075.4:c.17_18delCGinsTC
• TPCN2 p.Ala6Val

Variant summary

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

The NM_139075.4(TPCN2):​c.17_18delCGinsTC​(p.Ala6Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A6T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TPCN2 NM_139075.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 0 publications found

Genes affected

TPCN2 (HGNC:20820): (two pore segment channel 2) This gene encodes a putative cation-selective ion channel with two repeats of a six-transmembrane-domain. The protein localizes to lysosomal membranes and enables nicotinic acid adenine dinucleotide phosphate (NAADP) -induced calcium ion release from lysosome-related stores. This ubiquitously expressed gene has elevated expression in liver and kidney. Two common nonsynonymous SNPs in this gene strongly associate with blond versus brown hair pigmentation.[provided by RefSeq, Dec 2009]

TPCN2 Gene-Disease associations (from GenCC):

• albinism

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139075.4. 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
	TPCN2	NM_139075.4	MANE Select	c.17_18delCGinsTC	p.Ala6Val	missense	N/A	NP_620714.2	Q8NHX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPCN2	ENST00000294309.8	TSL:1 MANE Select	c.17_18delCGinsTC	p.Ala6Val	missense	N/A	ENSP00000294309.3	Q8NHX9
	TPCN2	ENST00000897239.1		c.17_18delCGinsTC	p.Ala6Val	missense	N/A	ENSP00000567298.1
	TPCN2	ENST00000897242.1		c.17_18delCGinsTC	p.Ala6Val	missense	N/A	ENSP00000567301.1

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.71

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-68816482;