rs12905120

Variant names:

• chr15-50642146-T-C
• rs12905120
• NM_017672.6:c.535+1194A>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.535+1194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,156 control chromosomes in the GnomAD database, including 571 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 0.078 (571 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 1 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
• macrothrombocytopenia, isolated

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	NM_017672.6	MANE Select	c.535+1194A>G		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.535+1194A>G		intron	N/A	NP_001288141.1	H0YLN8
	TRPM7	NR_149152.2		n.799+1194A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.535+1194A>G		intron	N/A	ENSP00000495860.1	Q96QT4
	TRPM7	ENST00000560955.5	TSL:1	c.535+1194A>G		intron	N/A	ENSP00000453277.1	H0YLN8

Frequencies

GnomAD3 genomes AF: 0.0777 AC: 11809 AN: 152038 Hom.: 569 Cov.: 32

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0777 AC: 11822 AN: 152156 Hom.: 571 Cov.: 32 AF XY: 0.0761 AC XY: 5665 AN XY: 74414

African (AFR) AF: 0.0304 AC: 1263 AN: 41558

American (AMR) AF: 0.0653 AC: 998 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.0983 AC: 510 AN: 5188

South Asian (SAS) AF: 0.122 AC: 587 AN: 4828

European-Finnish (FIN) AF: 0.0530 AC: 562 AN: 10606

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7355 AN: 67914

Other (OTH) AF: 0.0824 AC: 174 AN: 2112

Alfa AF: 0.0848 Hom.: 72

Bravo AF: 0.0737

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.038
DANN	Benign	0.21
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs12905120;

hg19: chr15-50934343;