rs11635825

Variant names:

• chr15-50662750-T-C
• rs11635825
• NM_017672.6:c.83+217A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017672.6(TRPM7):​c.83+217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,130 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1492 hom., cov: 32)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.751
• Publications: 9 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)

LOC128092252 (HGNC:0):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-50662750-T-C is Benign according to our data. Variant chr15-50662750-T-C is described in ClinVar as Benign. ClinVar VariationId is 1232550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 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.83+217A>G		intron	N/A	NP_060142.3
	LOC128092252	NM_001414947.1	MANE Select	c.267+217A>G		intron	N/A	NP_001401876.1	A0A6Q8PGL7
	TRPM7	NM_001301212.2		c.83+217A>G		intron	N/A	NP_001288141.1	H0YLN8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.83+217A>G		intron	N/A	ENSP00000495860.1	Q96QT4
	ENSG00000288645	ENST00000676296.1	MANE Select	c.267+217A>G		intron	N/A	ENSP00000502268.1	A0A6Q8PGL7
	TRPM7	ENST00000560955.5	TSL:1	c.83+217A>G		intron	N/A	ENSP00000453277.1	H0YLN8

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20994 AN: 152012 Hom.: 1491 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.138 AC: 21016 AN: 152130 Hom.: 1492 Cov.: 32 AF XY: 0.135 AC XY: 10064 AN XY: 74380

African (AFR) AF: 0.144 AC: 5957 AN: 41498

American (AMR) AF: 0.122 AC: 1867 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3468

East Asian (EAS) AF: 0.0998 AC: 517 AN: 5182

South Asian (SAS) AF: 0.166 AC: 800 AN: 4820

European-Finnish (FIN) AF: 0.0669 AC: 709 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10118 AN: 67992

Other (OTH) AF: 0.150 AC: 317 AN: 2110

Alfa AF: 0.145 Hom.: 1692

Bravo AF: 0.139

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.54
PhyloP100		-0.75
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: rs11635825; hg19: chr15-50954947;