Variant 15-50583143-TCTA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 3P and 10B. PM1PM4_SupportingBP6_ModerateBA1

The NM_017672.6(TRPM7):c.4500_4502del(p.Ser1500del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00387 in 1,604,776 control chromosomes in the GnomAD database, including 213 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 116 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 97 hom. )

Consequence

TRPM7
NM_017672.6 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.19

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity TRPM7_HUMAN

PM4

Nonframeshift variant in NON repetitive region in NM_017672.6. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 15-50583143-TCTA-T is Benign according to our data. Variant chr15-50583143-TCTA-T is described in ClinVar as [Benign]. Clinvar id is 3056286.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.069 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPM7	NM_017672.6 linkuse as main transcript	c.4500_4502del	p.Ser1500del	inframe_deletion	29/39	ENST00000646667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TRPM7	ENST00000646667.1 linkuse as main transcript	c.4500_4502del	p.Ser1500del	inframe_deletion	29/39		NM_017672.6	A1
TRPM7	ENST00000560955.5 linkuse as main transcript	c.4497_4499del	p.Ser1499del	inframe_deletion	29/39	1		P4
TRPM7	ENST00000560849.2 linkuse as main transcript	n.202_204del		non_coding_transcript_exon_variant	2/6	3
TRPM7	ENST00000645282.1 linkuse as main transcript	n.301_303del		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.0202

AC:

3074

AN:

152078

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0712

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00535

AC:

1297

AN:

242518

Hom.:

AF XY:

0.00438

AC XY:

576

AN XY:

131646

show subpopulations

Gnomad AFR exome

AF:

0.0699

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000580

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000135

Gnomad OTH exome

AF:

0.00221

GnomAD4 exome

AF:

0.00216

AC:

3134

AN:

1452580

Hom.:

AF XY:

0.00197

AC XY:

1424

AN XY:

722396

show subpopulations

Gnomad4 AFR exome

AF:

0.0720

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000355

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000748

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.0203

AC:

3084

AN:

152196

Hom.:

116

Cov.:

AF XY:

0.0197

AC XY:

1468

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0712

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.00395

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.0227

Asia WGS

AF:

0.0150

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TRPM7-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 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

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