rs3109894

Positions:

• chr15-50586377-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.4486+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,521,494 control chromosomes in the GnomAD database, including 128,565 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 (11658 hom., cov: 32)
  • Exomes 𝑓: 0.41 (116907 hom.)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.372

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 = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM7	NM_017672.6	c.4486+15C>T		intron_variant		ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPM7	ENST00000646667.1	c.4486+15C>T		intron_variant			NM_017672.6	A1
TRPM7	ENST00000560955.5	c.4486+15C>T		intron_variant		1		P4
TRPM7	ENST00000560849.2	n.191+15C>T		intron_variant, non_coding_transcript_variant		3
TRPM7	ENST00000645282.1	n.290+15C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58097 AN: 151804 Hom.: 11654 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.431

GnomAD3 exomes AF: 0.423 AC: 103622 AN: 245082 Hom.: 22425 AF XY: 0.422 AC XY: 56182 AN XY: 132994

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.480

Gnomad SAS exome AF: 0.411

Gnomad FIN exome AF: 0.406

Gnomad NFE exome AF: 0.415

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.411 AC: 562845 AN: 1369572 Hom.: 116907 Cov.: 21 AF XY: 0.412 AC XY: 282791 AN XY: 686934

Gnomad4 AFR exome AF: 0.270

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.420

Gnomad4 SAS exome AF: 0.418

Gnomad4 FIN exome AF: 0.413

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.383 AC: 58129 AN: 151922 Hom.: 11658 Cov.: 32 AF XY: 0.387 AC XY: 28715 AN XY: 74242

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.425

Alfa AF: 0.391 Hom.: 2965

Bravo AF: 0.387

Asia WGS AF: 0.372 AC: 1290 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.23

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: rs3109894; hg19: chr15-50878574;