rs17645523

Positions:

• chr15-50590448-T-C

Variant summary

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

The NM_017672.6(TRPM7):​c.4325-792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,994 control chromosomes in the GnomAD database, including 11,550 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 0.38 (11550 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM7	NM_017672.6	c.4325-792A>G		intron_variant		ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM7	ENST00000646667.1	c.4325-792A>G		intron_variant			NM_017672.6	A1
TRPM7	ENST00000560955.5	c.4325-792A>G		intron_variant		1		P4
TRPM7	ENST00000645282.1	n.129-792A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57640 AN: 151876 Hom.: 11552 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.379 AC: 57663 AN: 151994 Hom.: 11550 Cov.: 32 AF XY: 0.383 AC XY: 28490 AN XY: 74298

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.421

Alfa AF: 0.391 Hom.: 2378

Bravo AF: 0.384

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.61

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: rs17645523; hg19: chr15-50882645;