NM_017672.6:c.3164-1046C>G

Variant names:

• chr15-50597427-G-C
• rs7174839
• NM_017672.6:c.3164-1046C>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.3164-1046C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,068 control chromosomes in the GnomAD database, including 16,572 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 0.46 (16572 hom., cov: 33)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.3164-1046C>G		intron_variant	Intron 22 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.3164-1046C>G		intron_variant	Intron 22 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.3164-1046C>G		intron_variant	Intron 22 of 38	1		ENSP00000453277.1
TRPM7	ENST00000560284.1	n.545-1046C>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70551 AN: 151950 Hom.: 16567 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.464 AC: 70593 AN: 152068 Hom.: 16572 Cov.: 33 AF XY: 0.466 AC XY: 34659 AN XY: 74336

African (AFR) AF: 0.465 AC: 19306 AN: 41486

American (AMR) AF: 0.552 AC: 8437 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1649 AN: 3472

East Asian (EAS) AF: 0.471 AC: 2440 AN: 5176

South Asian (SAS) AF: 0.437 AC: 2106 AN: 4824

European-Finnish (FIN) AF: 0.420 AC: 4432 AN: 10546

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30523 AN: 67964

Other (OTH) AF: 0.505 AC: 1068 AN: 2116

Alfa AF: 0.444 Hom.: 1847

Bravo AF: 0.476

Asia WGS AF: 0.409 AC: 1422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.024
DANN	Benign	0.48
PhyloP100		-2.1
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: rs7174839; hg19: chr15-50889624;