15-50605476-T-C

Variant names:

• chr15-50605476-T-C
• rs17520350
• NM_017672.6:c.2710-332A>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.2710-332A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,258 control chromosomes in the GnomAD database, including 2,212 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 0.15 (2212 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.273 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.2710-332A>G		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.2710-332A>G		intron	N/A	NP_001288141.1
	TRPM7	NR_149152.2		n.2974-332A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.2710-332A>G		intron	N/A	ENSP00000495860.1
	TRPM7	ENST00000560955.5	TSL:1	c.2710-332A>G		intron	N/A	ENSP00000453277.1
	TRPM7	ENST00000560638.1	TSL:1	c.1321-332A>G		intron	N/A	ENSP00000452873.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22228 AN: 152140 Hom.: 2213 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.00288

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.146 AC: 22226 AN: 152258 Hom.: 2212 Cov.: 32 AF XY: 0.146 AC XY: 10887 AN XY: 74454

African (AFR) AF: 0.0397 AC: 1650 AN: 41574

American (AMR) AF: 0.280 AC: 4278 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5192

South Asian (SAS) AF: 0.204 AC: 985 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1389 AN: 10606

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12562 AN: 67988

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.0673 Hom.: 85

Bravo AF: 0.153

Asia WGS AF: 0.0890 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.65
PhyloP100		-0.86
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: rs17520350; hg19: chr15-50897673;