rs7163283

Variant names:

• chr15-50623901-A-G
• rs7163283
• NM_017672.6:c.1440+265T>C

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.1440+265T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,856 control chromosomes in the GnomAD database, including 26,964 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.59 (26964 hom., cov: 30)
• Consequence: TRPM7 NM_017672.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.623
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 15-50623901-A-G is Benign according to our data. Variant chr15-50623901-A-G is described in ClinVar as Benign. ClinVar VariationId is 1252425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 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.1440+265T>C		intron	N/A	NP_060142.3
	TRPM7	NM_001301212.2		c.1440+265T>C		intron	N/A	NP_001288141.1	H0YLN8
	TRPM7	NR_149152.2		n.1704+265T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPM7	ENST00000646667.1	MANE Select	c.1440+265T>C		intron	N/A	ENSP00000495860.1	Q96QT4
	TRPM7	ENST00000560955.5	TSL:1	c.1440+265T>C		intron	N/A	ENSP00000453277.1	H0YLN8
	TRPM7	ENST00000560638.1	TSL:1	c.51+265T>C		intron	N/A	ENSP00000452873.1	A0A0C4DGL2

Frequencies

GnomAD3 genomes AF: 0.593 AC: 89935 AN: 151736 Hom.: 26944 Cov.: 30

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.570

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.593 AC: 90008 AN: 151856 Hom.: 26964 Cov.: 30 AF XY: 0.591 AC XY: 43888 AN XY: 74224

African (AFR) AF: 0.665 AC: 27555 AN: 41406

American (AMR) AF: 0.633 AC: 9668 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1925 AN: 3470

East Asian (EAS) AF: 0.570 AC: 2940 AN: 5162

South Asian (SAS) AF: 0.558 AC: 2689 AN: 4816

European-Finnish (FIN) AF: 0.474 AC: 4989 AN: 10518

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38216 AN: 67904

Other (OTH) AF: 0.612 AC: 1291 AN: 2108

Alfa AF: 0.567 Hom.: 3158

Bravo AF: 0.608

Asia WGS AF: 0.562 AC: 1952 AN: 3474

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	-0.97
CADD	Benign	0.62
DANN	Benign	0.45
PhyloP100		-0.62
PromoterAI		0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99
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: rs7163283; hg19: chr15-50916098;