rs12899074

Positions:

• chr15-50649787-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017672.6(TRPM7):​c.123-902C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 152,198 control chromosomes in the GnomAD database, including 574 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 0.080 (574 hom., cov: 30)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

Genes affected

LOC128092252 (HGNC:):

TRPM7 (HGNC:17994): (transient receptor potential cation channel subfamily M member 7) This gene belongs to the melastatin subfamily of transient receptor potential family of ion channels. The protein encoded by this gene is both an ion channel and a serine/threonine protein kinase. The kinase activity is essential for the ion channel function, which serves to increase intracellular calcium levels and to help regulate magnesium ion homeostasis. The encoded protein is involved in cytoskeletal organization, cell adhesion, cell migration and organogenesis. Defects in this gene are a cause of amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam. The gene may also be associated with defects of cardiac function. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC128092252	NM_001414947.1	c.307-902C>T		intron_variant		ENST00000676296.1	NP_001401876.1
TRPM7	NM_017672.6	c.123-902C>T		intron_variant		ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.123-902C>T		intron_variant			NM_017672.6	ENSP00000495860	A1
	ENST00000676296.1	c.307-902C>T		intron_variant			NM_001414947.1	ENSP00000502268	P1
TRPM7	ENST00000560955.5	c.123-902C>T		intron_variant		1		ENSP00000453277	P4

Frequencies

GnomAD3 genomes AF: 0.0795 AC: 12090 AN: 152080 Hom.: 572 Cov.: 30

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0662

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.0795 AC: 12106 AN: 152198 Hom.: 574 Cov.: 30 AF XY: 0.0778 AC XY: 5789 AN XY: 74412

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.0663

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0853

Alfa AF: 0.0851 Hom.: 85

Bravo AF: 0.0760

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs12899074; hg19: chr15-50941984;