21-44417953-AC-CG

Variant names:

• chr21-44417953-AC-CG
• NM_003307.4:c.3173_3174delACinsCG
• TRPM2 p.His1058Pro

Variant summary

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

The NM_003307.4(TRPM2):​c.3173_3174delACinsCG​(p.His1058Pro) variant causes a missense change. 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. H1058Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRPM2 NM_003307.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.79
• Publications: 0 publications found

Genes affected

TRPM2 (HGNC:12339): (transient receptor potential cation channel subfamily M member 2) The protein encoded by this gene forms a tetrameric cation channel that is permeable to calcium, sodium, and potassium and is regulated by free intracellular ADP-ribose. The encoded protein is activated by oxidative stress and confers susceptibility to cell death. Alternative splicing results in multiple transcript variants encoding distinct protein isoforms. Additional transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2016]

TRPM2-AS (HGNC:50758): (TRPM2 antisense RNA)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003307.4. 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
	TRPM2	NM_003307.4	MANE Select	c.3173_3174delACinsCG	p.His1058Pro	missense	N/A	NP_003298.2	O94759-1
	TRPM2	NM_001320350.2		c.3173_3174delACinsCG	p.His1058Pro	missense	N/A	NP_001307279.2	E9PGK7
	TRPM2	NM_001433516.1		c.3173_3174delACinsCG	p.His1058Pro	missense	N/A	NP_001420445.1	O94759-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM2	ENST00000397928.6	TSL:1 MANE Select	c.3173_3174delACinsCG	p.His1058Pro	missense	N/A	ENSP00000381023.1	O94759-1
	TRPM2	ENST00000397932.6	TSL:1	c.3173_3174delACinsCG	p.His1058Pro	missense	N/A	ENSP00000381026.2	E9PGK7
	TRPM2	ENST00000300482.9	TSL:1	c.3173_3174delACinsCG	p.His1058Pro	missense	N/A	ENSP00000300482.5	O94759-1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8

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: chr21-45837836;