Variant 15-50570160-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017672.6(TRPM7):c.5309-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 1,584,076 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 31)

Exomes 𝑓: 0.010 ( 102 hom. )

Consequence

TRPM7
NM_017672.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001167

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.63

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 15-50570160-A-G is Benign according to our data. Variant chr15-50570160-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645329.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-50570160-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM7	NM_017672.6 linkuse as main transcript	c.5309-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000646667.1	NP_060142.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPM7	ENST00000646667.1 linkuse as main transcript	c.5309-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_017672.6	ENSP00000495860	A1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

992

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0159

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00656

AC:

1546

AN:

235820

Hom.:

AF XY:

0.00636

AC XY:

817

AN XY:

128370

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00238

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00177

Gnomad FIN exome

AF:

0.0176

Gnomad NFE exome

AF:

0.00922

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.0103

AC:

14733

AN:

1431772

Hom.:

102

Cov.:

AF XY:

0.00992

AC XY:

7069

AN XY:

712296

show subpopulations

Gnomad4 AFR exome

AF:

0.00130

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00203

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00902

GnomAD4 genome

AF:

0.00651

AC:

991

AN:

152304

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

485

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0159

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00826

Hom.:

Bravo

AF:

0.00542

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

TRPM7: BP4, BS2 -

TRPM7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 12, 2019

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

-0.79

CADD

Benign

3.6

DANN

Benign

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.094

SpliceAI score (max)

0.020

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