chr15-50647057-C-A

Variant names:

• chr15-50647057-C-A
• rs2899462
• NM_017672.6:c.321+1630G>T

Variant summary

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

The NM_017672.6(TRPM7):​c.321+1630G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,134 control chromosomes in the GnomAD database, including 10,041 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 0.33 (10041 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.464 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.321+1630G>T		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.321+1630G>T		intron	N/A	NP_001288141.1
	TRPM7	NR_149152.2		n.585+1630G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.321+1630G>T		intron	N/A	ENSP00000495860.1
	TRPM7	ENST00000560955.5	TSL:1	c.321+1630G>T		intron	N/A	ENSP00000453277.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50022 AN: 152016 Hom.: 10044 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.396

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

GnomAD4 genome AF: 0.329 AC: 50028 AN: 152134 Hom.: 10041 Cov.: 32 AF XY: 0.335 AC XY: 24928 AN XY: 74368

African (AFR) AF: 0.0903 AC: 3754 AN: 41554

American (AMR) AF: 0.474 AC: 7238 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1333 AN: 3472

East Asian (EAS) AF: 0.463 AC: 2395 AN: 5168

South Asian (SAS) AF: 0.387 AC: 1868 AN: 4828

European-Finnish (FIN) AF: 0.407 AC: 4303 AN: 10564

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.408 AC: 27721 AN: 67948

Other (OTH) AF: 0.390 AC: 824 AN: 2112

Alfa AF: 0.215 Hom.: 557

Bravo AF: 0.327

Asia WGS AF: 0.349 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.60
PhyloP100		0.29
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: rs2899462; hg19: chr15-50939254;