rs17645523

Variant names:

• chr15-50590448-T-C
• rs17645523
• NM_017672.6:c.4325-792A>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.4325-792A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,994 control chromosomes in the GnomAD database, including 11,550 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 (11550 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.894
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM7	NM_017672.6	c.4325-792A>G		intron_variant	Intron 26 of 38	ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1	c.4325-792A>G		intron_variant	Intron 26 of 38		NM_017672.6	ENSP00000495860.1
TRPM7	ENST00000560955.5	c.4325-792A>G		intron_variant	Intron 26 of 38	1		ENSP00000453277.1
TRPM7	ENST00000645282.1	n.129-792A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57640 AN: 151876 Hom.: 11552 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.426

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

GnomAD4 genome AF: 0.379 AC: 57663 AN: 151994 Hom.: 11550 Cov.: 32 AF XY: 0.383 AC XY: 28490 AN XY: 74298

African (AFR) AF: 0.263 AC: 10916 AN: 41468

American (AMR) AF: 0.488 AC: 7450 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1337 AN: 3468

East Asian (EAS) AF: 0.469 AC: 2424 AN: 5172

South Asian (SAS) AF: 0.393 AC: 1898 AN: 4824

European-Finnish (FIN) AF: 0.406 AC: 4284 AN: 10544

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

European-Non Finnish (NFE) AF: 0.410 AC: 27874 AN: 67942

Other (OTH) AF: 0.421 AC: 889 AN: 2114

Alfa AF: 0.391 Hom.: 2378

Bravo AF: 0.384

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.61
PhyloP100		0.89
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: rs17645523; hg19: chr15-50882645;