rs2163098

Variant names:

• chr15-50614301-C-G
• rs2163098
• NM_017672.6:c.1495-38G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017672.6(TRPM7):​c.1495-38G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 1,545,672 control chromosomes in the GnomAD database, including 1,065 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 0.029 (90 hom., cov: 32)
  • Exomes 𝑓: 0.034 (975 hom.)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 3 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=-0.82).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.1495-38G>C		intron_variant	Intron 13 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.1495-38G>C		intron_variant	Intron 13 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.1495-38G>C		intron_variant	Intron 13 of 38	1		ENSP00000453277.1
TRPM7	ENST00000560638.1	c.106-38G>C		intron_variant	Intron 2 of 9	1		ENSP00000452873.1

Frequencies

GnomAD3 genomes AF: 0.0287 AC: 4363 AN: 152130 Hom.: 90 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0451

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0245

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0366

Gnomad OTH AF: 0.0426

GnomAD2 exomes AF: 0.0316 AC: 6461 AN: 204634 AF XY: 0.0330

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.000185

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0393

Gnomad OTH exome AF: 0.0418

GnomAD4 exome AF: 0.0339 AC: 47256 AN: 1393424 Hom.: 975 Cov.: 26 AF XY: 0.0346 AC XY: 23896 AN XY: 691242

African (AFR) AF: 0.0118 AC: 365 AN: 31058

American (AMR) AF: 0.0345 AC: 1195 AN: 34656

Ashkenazi Jewish (ASJ) AF: 0.0860 AC: 1930 AN: 22438

East Asian (EAS) AF: 0.000128 AC: 5 AN: 39196

South Asian (SAS) AF: 0.0287 AC: 2179 AN: 76026

European-Finnish (FIN) AF: 0.0110 AC: 564 AN: 51050

Middle Eastern (MID) AF: 0.0788 AC: 430 AN: 5454

European-Non Finnish (NFE) AF: 0.0358 AC: 38473 AN: 1075988

Other (OTH) AF: 0.0367 AC: 2115 AN: 57558

GnomAD4 genome AF: 0.0286 AC: 4359 AN: 152248 Hom.: 90 Cov.: 32 AF XY: 0.0283 AC XY: 2105 AN XY: 74436

African (AFR) AF: 0.0123 AC: 512 AN: 41552

American (AMR) AF: 0.0450 AC: 687 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.0245 AC: 118 AN: 4822

European-Finnish (FIN) AF: 0.0124 AC: 131 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0366 AC: 2490 AN: 68024

Other (OTH) AF: 0.0422 AC: 89 AN: 2110

Alfa AF: 0.0378 Hom.: 26

Bravo AF: 0.0296

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.47
DANN	Benign	0.54
PhyloP100		-0.79
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: rs2163098; hg19: chr15-50906498;