Variant 9-74792667-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_017662.5(TRPM6):c.2495A>G(p.Tyr832Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

TRPM6
NM_017662.5 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.05

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 9-74792667-T-C is Pathogenic according to our data. Variant chr9-74792667-T-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 403726.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPM6	NM_017662.5 linkuse as main transcript	c.2495A>G	p.Tyr832Cys	missense_variant	19/39	ENST00000360774.6	NP_060132.3	Q9BX84-1
TRPM6	NM_001177310.2 linkuse as main transcript	c.2480A>G	p.Tyr827Cys	missense_variant	19/39		NP_001170781.1	Q9BX84-2
TRPM6	NM_001177311.2 linkuse as main transcript	c.2480A>G	p.Tyr827Cys	missense_variant	19/39		NP_001170782.1	Q9BX84-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRPM6	ENST00000360774.6 linkuse as main transcript	c.2495A>G	p.Tyr832Cys	missense_variant	19/39	1	NM_017662.5	ENSP00000354006.1	Q9BX84-1
TRPM6	ENST00000361255.7 linkuse as main transcript	c.2480A>G	p.Tyr827Cys	missense_variant	19/39	1		ENSP00000354962.3	Q9BX84-3
TRPM6	ENST00000449912.6 linkuse as main transcript	c.2480A>G	p.Tyr827Cys	missense_variant	19/39	1		ENSP00000396672.2	Q9BX84-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intestinal hypomagnesemia 1

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Shenzhen Institute of Pediatrics, Shenzhen Children's Hospital

Mar 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

.;.;D

Eigen

Benign

-0.015

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.8

.;.;L

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.59

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.021

B;.;B

Vest4

0.47

MutPred

0.58

.;.;Gain of helix (P = 0.0349);

MVP

0.95

MPC

0.33

ClinPred

0.83

GERP RS

5.9

Varity_R

0.22

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.67

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.67

Position offset: 1

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