Variant 15-50574885-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_017672.6(TRPM7):c.4986C>T(p.Tyr1662Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,610,592 control chromosomes in the GnomAD database, including 256,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26797 hom., cov: 33)

Exomes 𝑓: 0.56 ( 229330 hom. )

Consequence

TRPM7
NM_017672.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.07

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 15-50574885-G-A is Benign according to our data. Variant chr15-50574885-G-A is described in ClinVar as [Benign]. Clinvar id is 1256704.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 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.4986C>T	p.Tyr1662Tyr	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.4986C>T	p.Tyr1662Tyr	synonymous_variant	34/39		NM_017672.6	ENSP00000495860.1		Q96QT4

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89712

AN:

151942

Hom.:

26777

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.632

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.475

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.614

GnomAD3 exomes

AF:

0.570

AC:

141859

AN:

248956

Hom.:

40905

AF XY:

0.569

AC XY:

76918

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.624

Gnomad ASJ exome

AF:

0.549

Gnomad EAS exome

AF:

0.555

Gnomad SAS exome

AF:

0.571

Gnomad FIN exome

AF:

0.471

Gnomad NFE exome

AF:

0.563

Gnomad OTH exome

AF:

0.566

GnomAD4 exome

AF:

0.559

AC:

815161

AN:

1458530

Hom.:

229330

Cov.:

AF XY:

0.560

AC XY:

406343

AN XY:

725754

show subpopulations

Gnomad4 AFR exome

AF:

0.670

Gnomad4 AMR exome

AF:

0.621

Gnomad4 ASJ exome

AF:

0.551

Gnomad4 EAS exome

AF:

0.558

Gnomad4 SAS exome

AF:

0.573

Gnomad4 FIN exome

AF:

0.480

Gnomad4 NFE exome

AF:

0.555

Gnomad4 OTH exome

AF:

0.565

GnomAD4 genome

AF:

0.590

AC:

89785

AN:

152062

Hom.:

26797

Cov.:

AF XY:

0.589

AC XY:

43804

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.632

Gnomad4 ASJ

AF:

0.555

Gnomad4 EAS

AF:

0.570

Gnomad4 SAS

AF:

0.560

Gnomad4 FIN

AF:

0.475

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.611

Alfa

AF:

0.565

Hom.:

20363

Bravo

AF:

0.605

Asia WGS

AF:

0.561

AC:

1950

AN:

3478

EpiCase

AF:

0.580

EpiControl

AF:

0.583

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.2

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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