rs7859201

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_017662.5(TRPM6):c.2124T>G(p.Leu708Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,613,550 control chromosomes in the GnomAD database, including 129,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 17381 hom., cov: 30)

Exomes 𝑓: 0.39 ( 112231 hom. )

Consequence

TRPM6
NM_017662.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.390

Variant links:

Genes affected

TRPM6 (HGNC:17995): (transient receptor potential cation channel subfamily M member 6) This gene is predominantly expressed in the kidney and colon, and encodes a protein containing an ion channel domain and a protein kinase domain. It is crucial for magnesium homeostasis, and plays an essential role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Mutations in this gene are associated with hypomagnesemia with secondary hypocalcemia. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Apr 2010]

TRPM6 links:

RN7SKP47 (HGNC:45771): (RN7SK pseudogene 47)

RN7SKP47 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 9-74800368-A-C is Benign according to our data. Variant chr9-74800368-A-C is described in ClinVar as [Benign]. Clinvar id is 367318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-74800368-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPM6	NM_017662.5 link	c.2124T>G	p.Leu708Leu	synonymous_variant	Exon 17 of 39	ENST00000360774.6	NP_060132.3	Q9BX84-1
TRPM6	NM_001177310.2 link	c.2109T>G	p.Leu703Leu	synonymous_variant	Exon 17 of 39		NP_001170781.1	Q9BX84-2
TRPM6	NM_001177311.2 link	c.2109T>G	p.Leu703Leu	synonymous_variant	Exon 17 of 39		NP_001170782.1	Q9BX84-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPM6	ENST00000360774.6 link	c.2124T>G	p.Leu708Leu	synonymous_variant	Exon 17 of 39	1	NM_017662.5	ENSP00000354006.1	Q9BX84-1
TRPM6	ENST00000361255.7 link	c.2109T>G	p.Leu703Leu	synonymous_variant	Exon 17 of 39	1		ENSP00000354962.3	Q9BX84-3
TRPM6	ENST00000449912.6 link	c.2109T>G	p.Leu703Leu	synonymous_variant	Exon 17 of 39	1		ENSP00000396672.2	Q9BX84-2
RN7SKP47	ENST00000365347.1 link	n.*146A>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69495

AN:

151614

Hom.:

17356

Cov.:

show subpopulations

Gnomad AFR

AF:

0.668

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.353

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.338

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.397

AC:

99806

AN:

251414

Hom.:

20847

AF XY:

0.397

AC XY:

53947

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.681

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.408

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.388

AC:

567083

AN:

1461818

Hom.:

112231

Cov.:

AF XY:

0.388

AC XY:

282456

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.681

Gnomad4 AMR exome

AF:

0.297

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.368

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.411

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.395

GnomAD4 genome

AF:

0.459

AC:

69580

AN:

151732

Hom.:

17381

Cov.:

AF XY:

0.456

AC XY:

33793

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.668

Gnomad4 AMR

AF:

0.353

Gnomad4 ASJ

AF:

0.371

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.412

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.393

Hom.:

23948

Bravo

AF:

0.463

Asia WGS

AF:

0.388

AC:

1350

AN:

3478

EpiCase

AF:

0.370

EpiControl

AF:

0.376

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Intestinal hypomagnesemia 1

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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