15-50608409-G-C

Variant names:

• chr15-50608409-G-C
• rs17520378
• NM_017672.6:c.2581-1081C>G

Variant summary

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

The NM_017672.6(TRPM7):​c.2581-1081C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,158 control chromosomes in the GnomAD database, including 1,903 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 0.13 (1903 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	NM_017672.6	MANE Select	c.2581-1081C>G		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.2581-1081C>G		intron	N/A	NP_001288141.1
	TRPM7	NR_149152.2		n.2845-1081C>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.2581-1081C>G		intron	N/A	ENSP00000495860.1
	TRPM7	ENST00000560955.5	TSL:1	c.2581-1081C>G		intron	N/A	ENSP00000453277.1
	TRPM7	ENST00000560638.1	TSL:1	c.1192-1081C>G		intron	N/A	ENSP00000452873.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20236 AN: 152040 Hom.: 1904 Cov.: 32

Gnomad AFR AF: 0.0338

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.133 AC: 20237 AN: 152158 Hom.: 1903 Cov.: 32 AF XY: 0.130 AC XY: 9654 AN XY: 74384

African (AFR) AF: 0.0337 AC: 1398 AN: 41530

American (AMR) AF: 0.0887 AC: 1355 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5194

South Asian (SAS) AF: 0.114 AC: 551 AN: 4816

European-Finnish (FIN) AF: 0.184 AC: 1943 AN: 10568

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 290

European-Non Finnish (NFE) AF: 0.200 AC: 13592 AN: 67988

Other (OTH) AF: 0.136 AC: 287 AN: 2112

Alfa AF: 0.105 Hom.: 196

Bravo AF: 0.120

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.65
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17520378; hg19: chr15-50900606;