rs3131583

Positions:

• chr15-50556799-A-G

Variant summary

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

The ENST00000561267.5(TRPM7):​c.605-4102T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,206 control chromosomes in the GnomAD database, including 3,322 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 0.18 (3322 hom., cov: 33)
• Consequence: TRPM7 ENST00000561267.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.463

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.50556799A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000561267.5	c.605-4102T>C		intron_variant		3		ENSP00000454066.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27977 AN: 152086 Hom.: 3325 Cov.: 33

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.184 AC: 27973 AN: 152206 Hom.: 3322 Cov.: 33 AF XY: 0.191 AC XY: 14215 AN XY: 74424

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.207

Alfa AF: 0.218 Hom.: 7688

Bravo AF: 0.173

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.2
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3131583; hg19: chr15-50848996;