Variant 15-50574945-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_017672.6(TRPM7):c.4926G>A(p.Gly1642Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0473 in 1,613,802 control chromosomes in the GnomAD database, including 2,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.080 ( 808 hom., cov: 32)

Exomes 𝑓: 0.044 ( 2039 hom. )

Consequence

TRPM7
NM_017672.6 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0480

Variant links:

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 links:

TRPM7 (HGNC:):

TRPM7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 15-50574945-C-T is Benign according to our data. Variant chr15-50574945-C-T is described in ClinVar as [Benign]. Clinvar id is 3056472.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.048 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM7	NM_017672.6 linkuse as main transcript	c.4926G>A	p.Gly1642Gly	synonymous_variant	34/39	ENST00000646667.1	NP_060142.3	Q96QT4A0A024R5V1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1 linkuse as main transcript	c.4926G>A	p.Gly1642Gly	synonymous_variant	34/39		NM_017672.6	ENSP00000495860.1		Q96QT4

Frequencies

GnomAD3 genomes

AF:

0.0801

AC:

12179

AN:

152032

Hom.:

808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.184

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0617

Gnomad ASJ

AF:

0.0899

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.0441

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0404

Gnomad OTH

AF:

0.0796

GnomAD3 exomes

AF:

0.0484

AC:

12062

AN:

249418

Hom.:

527

AF XY:

0.0478

AC XY:

6463

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.189

Gnomad AMR exome

AF:

0.0386

Gnomad ASJ exome

AF:

0.0946

Gnomad EAS exome

AF:

0.00206

Gnomad SAS exome

AF:

0.0456

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.0429

Gnomad OTH exome

AF:

0.0507

GnomAD4 exome

AF:

0.0439

AC:

64116

AN:

1461652

Hom.:

2039

Cov.:

AF XY:

0.0440

AC XY:

32024

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0409

Gnomad4 ASJ exome

AF:

0.0960

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.0476

Gnomad4 FIN exome

AF:

0.0119

Gnomad4 NFE exome

AF:

0.0404

Gnomad4 OTH exome

AF:

0.0533

GnomAD4 genome

AF:

0.0801

AC:

12188

AN:

152150

Hom.:

808

Cov.:

AF XY:

0.0783

AC XY:

5822

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.184

Gnomad4 AMR

AF:

0.0616

Gnomad4 ASJ

AF:

0.0899

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0439

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0404

Gnomad4 OTH

AF:

0.0787

Alfa

AF:

0.0526

Hom.:

627

Bravo

AF:

0.0872

Asia WGS

AF:

0.0360

AC:

128

AN:

3478

EpiCase

AF:

0.0496

EpiControl

AF:

0.0526

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TRPM7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 11, 2023

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.5

DANN

Benign

0.65

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over