rs3109894

Variant names:

• chr15-50586377-G-A
• rs3109894
• NM_017672.6:c.4486+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-50586377-G-A
• chr15-50586377-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

TRPM7 Gene-Disease associations (from GenCC):

• hypomagnesemia, seizures, and intellectual disability

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• macrothrombocytopenia, isolated

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• amyotrophic lateral sclerosis-parkinsonism-dementia complex

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017672.6. 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
	TRPM7	NM_017672.6	MANE Select	c.4486+15C>T		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.4486+15C>T		intron	N/A	NP_001288141.1
	TRPM7	NR_149152.2		n.4700+15C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.4486+15C>T		intron	N/A	ENSP00000495860.1
	TRPM7	ENST00000560955.5	TSL:1	c.4486+15C>T		intron	N/A	ENSP00000453277.1
	TRPM7	ENST00000560849.2	TSL:3	n.191+15C>T		intron	N/A

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

GnomAD2 exomes AF: 0.423 AC: 103622 AN: 245082 AF XY: 0.422

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 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

African (AFR) AF: 0.270 AC: 8547 AN: 31704

American (AMR) AF: 0.514 AC: 22573 AN: 43898

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 9874 AN: 25548

East Asian (EAS) AF: 0.420 AC: 16449 AN: 39170

South Asian (SAS) AF: 0.418 AC: 35038 AN: 83776

European-Finnish (FIN) AF: 0.413 AC: 22000 AN: 53224

Middle Eastern (MID) AF: 0.410 AC: 2284 AN: 5572

European-Non Finnish (NFE) AF: 0.411 AC: 423128 AN: 1029348

Other (OTH) AF: 0.400 AC: 22952 AN: 57332

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

African (AFR) AF: 0.276 AC: 11427 AN: 41428

American (AMR) AF: 0.489 AC: 7474 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3468

East Asian (EAS) AF: 0.468 AC: 2423 AN: 5172

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4822

European-Finnish (FIN) AF: 0.408 AC: 4293 AN: 10522

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27789 AN: 67922

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.389 Hom.: 3005

Bravo AF: 0.387

Asia WGS AF: 0.372 AC: 1290 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.23
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3109894; hg19: chr15-50878574;